Research Guido De Meyer

Abstract

Chronic inflammation plays a significant role in both the onset and progression of many diseases, including, but not limited to, cardiovascular disease, chronic infections, cancer, and inflammatory organ diseases such as COPD, NAFLD, and IBD. Furthermore, acute infections may also trigger chronic inflammation and associated long lasting sequelae. As the prevalence of these diseases is increasing in Western societies and also emerging in other regions, research in this area can have a profound societal and scientific impact. Regulated cell death, barrier dysfunction, and immune modulation are key drivers of chronic inflammatory processes (Fig. 1). There is growing evidence for a limited number of common molecular pathways underpinning the regulation of these processes, and hence for a complex interplay in their pathophysiology. In this regard, Infla-Med brings together UAntwerp's leading basic and translational researchers in these three domains to form a bench-to-bedside and back consortium. The collaboration of complementary forces has enabled scientific breakthroughs in inflammation-focused research and has proven crucial in leveraging collaborations and funding in this competitive research field. For instance, Infla-Med's first 'stage' (2016-2019) resulted in more than € 23M in awarded funding with an overall stable 45% success rate since 2016. Moreover, halfway through Infla-Med's second 'stage' (2020-2022), we have already acquired the same amount of competitive grants. In terms of excellence, Infla-Med's principle investigators have achieved remarkable success in securing large, highly competitive grants for interdisciplinary research at local (BOF-GOA/IMPULS), national (FWO-EOS, iBOF), and international (ERA.Net, Innovative Medicines Initiative, coordination of H2020-MSCA-ITN and HE-MSCA-DN projects) levels. This shows that Infla-Med has established a very high-performing synergistic research framework among its principle investigators. The next 'stage' of Infla-Med will focus on discovering additional scientific breakthroughs and increasing our involvement in leading international research networks and acquiring international excellence funding (ERC). Four key strategic decisions support these ambitious aims for Infla-Med's next stage.

Researcher(s)

• Promoter: De Meyer Guido
• Co-promoter: Caljon Guy
• Co-promoter: De Meester Ingrid
• Co-promoter: De Winter Benedicte
• Co-promoter: Francque Sven
• Co-promoter: Segers Vincent
• Co-promoter: Smet Annemieke
• Co-promoter: Vanden Berghe Tom
• Co-promoter: Van Der Veken Pieter
• Co-promoter: Wullaert Andy

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

Life expectancy keeps increasing in developed countries. Because age is an important independent risk factor for cardiovascular disease (CVD), its impact on healthcare systems is substantial. Aging is accompanied by impaired autophagy, which triggers a strong interest in this highly conserved intracellular recycling process in various disease areas including CVD. We previously reported that impaired autophagy in vascular smooth muscle cells affects vasomotor function and accelerates the development of atherosclerotic plaques. However, the role of endothelial autophagy in vascular disease remains poorly understood, despite numerous studies indicating that endothelial autophagy maintains normal vessel wall biology. In this project, we would like to study in more depth the role and significance of endothelial autophagy in vascular disease by using an appropriate mouse model for defective autophagy in endothelial cells (ECs). Special attention will be given to how endothelial autophagy influences vascular reactivity, arterial stiffness, blood pressure and atherogenesis. A second aim is the prevention of vascular disease by stimulating autophagy selectively in ECs by using key autophagy inducers linked to an EC-specific homing peptide, thereby avoiding systemic side effects. The knowledge acquired within this project will allow a significant advance in the general understanding of autophagy (and its impaired function) in vascular disease.

Researcher(s)

• Promoter: Martinet Wim
• Co-promoter: De Meyer Guido

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

Life expectancy keeps increasing in developed countries. Because age is an important independent risk factor for cardiovascular disease (CVD), its impact on healthcare systems is substantial. Aging is accompanied by impaired autophagy, which triggers a strong interest in this highly conserved intracellular recycling process in various disease areas including CVD. We previously reported that impaired autophagy in vascular smooth muscle cells affects vasomotor function and accelerates the development of atherosclerotic plaques. However, the role of endothelial autophagy in vascular disease remains poorly understood, despite numerous studies indicating that endothelial autophagy maintains normal vessel wall biology. In this project, we would like to study in more depth the role and significance of endothelial autophagy in vascular disease by using an appropriate mouse model for defective autophagy in endothelial cells (ECs). Special attention will be given to how endothelial autophagy influences vascular reactivity, arterial stiffness, blood pressure and atherogenesis. A second aim is the prevention of vascular disease by stimulating autophagy selectively in ECs by using a key autophagy inducer linked to an EC-specific homing peptide, thereby avoiding systemic side effects. The knowledge acquired within this project will allow a significant advance in the general understanding of autophagy (and its impaired function) in vascular disease.

Researcher(s)

• Promoter: Martinet Wim
• Co-promoter: De Meyer Guido
• Fellow: Roeyen Eline

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

Acute cardiovascular syndromes (ACS) are the main cause of death in Western society and are caused by atherosclerosis. Intraplaque hemorrhage is a key characteristic of an unstable atherosclerotic plaque at risk for rupture. We propose here that therapeutic approaches to prevent the incidence of intraplaque hemorrhage is a powerful strategy to limit the incidence of ACS and reduce overall disease burden. Intraplaque hemorrhage is caused by leakage of intraplaque microvessels. We hypothesize that mast cells, a potent immune cell type, induce microvascular instability in advanced atherosclerosis and is causally involved in the incidence of intraplaque hemorrhage. We aim to a) elucidate how mast cells in atherosclerosis contribute to microvessel instability and hemorrhage and b) develop therapeutic strategies inhibiting mast cell induced vascular leakage to prevent intraplaque hemorrhage and subsequent ACS. we will gain novel insights in mast cell-induced intraplaque hemorrhage, and novel therapeutic intervention strategies to improve plaque stability and to limit the incidence of ACS.

Researcher(s)

• Promoter: De Meyer Guido

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

Cell death is a prominent feature of advanced plaques with a major impact on atherogenesis and plaque destabilization. According to morphological studies, the vast majority of dying cells in advanced human atherosclerotic plaques undergo necrotic cell death. Gasdermins have recently been identified as essential effector molecules in different types of programmed necrosis by forming pores in the plasma membrane. Besides the canonical caspase-1/inflammasome pathway that activates gasdermin D, gasdermin E was recently identified as an alternative key executioner of programmed necrosis after cleavage by caspase-3. Although numerous studies underscored the importance of caspase-3-mediated cell death in atherosclerosis, the role and impact of gasdermin E-mediated necrotic cell death is currently unknown. Nonetheless, necrosis has become an important and attractive research target to stabilize rupture-prone plaques. Therefore, this research proposal defines the following objectives: (1) extensive analysis of gasdermin E-mediated necrosis in both human and mouse plaques, (2) identification of the molecular mechanisms of gasdermin E-mediated necrosis in atherosclerosis, (3) inhibition of plaque necrosis using gasdermin E knockout mice, and (4) characterization of autophagy as a natural defense mechanism against gasdermin E-mediated necrosis. In general, this project will allow a significant advance in the fundamental understanding of regulated necrosis in atherosclerosis.

Researcher(s)

• Promoter: Martinet Wim
• Co-promoter: De Meyer Guido
• Fellow: Zurek Michelle

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

Morphological studies indicate that the vast majority of dying cells in advanced human atherosclerotic plaques undergo necrosis. Although the role of necrosis in atherosclerosis remains ill-defined, a growing body of evidence suggests that necrotic death stimulates atherogenesis and plaque instability through induction of inflammation and enlargement of a central necrotic core. For a long time, necrosis in advanced plaques has been considered as a merely accidental and uncontrolled form of cell death, but recent data indicate that it can also occur in a regulated fashion through induction of necroptosis. However, it should be noted that other examples of regulated necrosis such as ferroptosis are emerging. Moreover, gasdermins have recently been identified as essential effector molecules in different types of programmed necrosis by forming pores in the plasma membrane. Because regulated necrosis is considered an important pharmacological target to stabilize plaques, the following objectives are defined: (1) identification of ferroptosis and gasdermin E-mediated necrosis in both human and mouse plaques, (2) inhibition of both processes via genetic or pharmacological approaches, and (3) characterization of autophagy as a natural defense mechanism against necrosis in atherosclerosis. This project may lead to the discovery of novel anti-atherosclerosis therapies, and will allow a significant advance in the fundamental understanding of regulated necrosis in atherosclerosis.

Researcher(s)

• Promoter: Martinet Wim
• Co-promoter: De Meyer Guido

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

The Vevo LAZR-X is an imaging platform for preclinical applications capable of acquiring in vivo anatomical, functional and molecular data. It combines ultra high frequency ultrasound with photoacoustic imaging (a new biomedical imaging modality based on the use of lasergenerated ultrasound) for high resolution images as well as software for analysis and quantification. This equipment will be used in the context of the study of (cardio)vascular diseases, genetics of the heart, heart valves and aortic dissection, kidney diseases and their effects on the heart and blood vessels, and for cancer research.

Researcher(s)

• Promoter: De Meyer Guido
• Co-promoter: De Keulenaer Gilles
• Co-promoter: Heidbuchel Hein
• Co-promoter: Loeys Bart
• Co-promoter: Smits Evelien
• Co-promoter: Van Craenenbroeck Emeline
• Co-promoter: Verhulst Anja
• Co-promoter: Verstraeten Aline

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

Autophagy is crucial in the (patho)physiology, including inflammation, infection and cancer.Autophagy functions as a survival mechanism by maintaining viability during periods of stress, and byremoving damaged organelles and toxic metabolites, such as protein aggregates or intracellular pathogens. The Atlantis research consortium (AuTophagy in InfLAmmatioN and inflammaTory dISorders) brings together a team of expert investigators from the complementary fields of autophagy, (cancer) cell death signaling, inflammation signaling, angiogenesis and atherosclerosis, and drug screening and medicinal chemistry. We will study in an integrated way the impact of autophagy and its pharmacological modulation in various vascular diseases with a focus on the endothelium and its functional interaction with immune cells in sepsis, tumor-driven (lymph)angiogenesis, and atherosclerosis.

Researcher(s)

• Promoter: De Meyer Guido
• Co-promoter: Van Der Veken Pieter

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

The Research Consortium of Excellence Infla-Med combines multidisciplinary expertise of eight research groups from two faculties to perform fundamental and translational research on inflammation, including: inflammatory gastrointestinal, cardiovascular, lung and kidney disorders, sepsis and allergies, as well as parasitic diseases, thereby focusing on specific inflammatory cell populations, including monocytes/macrophages, mast cells, basophils and lymphocytes. The approach of the Infla-Med consortium is twofold. Firstly, fundamental studies are performed to unravel the pathophysiological mechanisms underlying inflammatory conditions in order to enable more rational, targeted and effective intervention strategies. Secondly, Infla-Med aims to identify and validate novel therapeutic targets by screening chemical compounds in early drug discovery studies and by using an extensive platform of in vitro assays and in vivo models. The close collaboration with the Antwerp University Hospital (UZA) creates the opportunity to directly translate and clinically validate experimental findings. Thereby, Infla-Med contributes to two Frontline Research Domains of the University of Antwerp: 'Drug Discovery and Development' and 'Infectious Diseases'. Over the past four years, the multidisciplinary collaborations within Infla-Med have proven to be very successful and productive. By integrating the Infla-Med unique expertise on drug development, in vitro assays and clinically relevant animal models (validated with human samples), significant competitive funding has been acquired at European, national and UAntwerp levels with a success rate of more than 45%, which is far above the (inter)national average. Noteworthy, several Infla-Med projects have also made the transition towards valorization, demonstrating that Infla-Med results obtained from both fundamental research and well-designed preclinical studies can successfully be translated into clinical trials.

Researcher(s)

• Promoter: De Meyer Guido
• Co-promoter: Augustyns Koen
• Co-promoter: Caljon Guy
• Co-promoter: De Meester Ingrid
• Co-promoter: De Winter Benedicte
• Co-promoter: Ebo Didier
• Co-promoter: Heidbuchel Hein
• Co-promoter: Vanden Berghe Tom

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project website

Project type(s)

• Research Project

Abstract

In the last century, the enormous improvements in life expectancy have led to a global population that has grown considerably older. The number of people over 65 is expected to increase from an estimated 524 million in 2010 to nearly 1.5 billion in 2050 (source WHO). Therefore, age-related diseases such as cardiovascular disease (CVD), diabetes, kidney disease and neurological disorders have a significant impact on our quality of life and represent a huge social and economic burden. Vascular ageing is characterized by structural and functional changes in the wall of large arteries, leading to arterial stiffness, which is an independent predictor of cardiovascular complications. Moreover, there is increasing evidence that it is a key driving force for multiple age-related cardiac, renal and cerebral pathologies. This challenge aims to better understand the pathophysiological mechanisms causing vascular ageing and arterial stiffness in order to prevent or delay this process and improve quality of life. The focus will be on the role of autophagy in vascular ageing, which is a homeostatic process that supports cell survival under stressful conditions. The autophagic process becomes impaired as we age, contributing to the development of age-related diseases. However, many questions about why autophagy declines and how it can be therapeutically targeted, still remain unanswered.

Researcher(s)

• Promoter: Roth Lynn
• Co-promoter: De Meyer Guido
• Co-promoter: Guns Pieter-Jan
• Co-promoter: Martinet Wim
• Fellow: Neutel Cédric

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

Crucial insights in cell and developmental biology have been gained by virtue of live cell imaging technology. Along with a growing complexity of cellular models and the finesse with which they can be genetically engineered, comes a demand for more advanced microscopy. In brief, modern comprehensive cell systems research (cellomics) requires light-efficient, intelligent and interactive imaging modalities. To address this shared need, our consortium has identified a state-of-the art platform that allows ultrafast, yet minimally invasive imaging of small to medium-sized biological samples (from single cells to organoids) at high resolution, so as to capture dynamic events that range in timescale from voltage fluctuations to successive cell divisions. To only focus on those events that are truly of interest, and thereby boost throughput, the system is equipped with online image recognition capabilities. Finally, to allow targeted perturbations such as local damage induction or optogenetic switching, small regions can be selectively illuminated in the field of view. With this level of control, it will become possible to interrogate (sub-)cellular processes with unprecedented detail. The platform readily finds applications in diverse frontline research fields including neuroscience, cardiovascular research and infectious diseases, rendering it an indispensable asset for the applicants, the microscopy core facility and the University of Antwerp.

Researcher(s)

• Promoter: De Vos Winnok
• Co-promoter: Caljon Guy
• Co-promoter: De Meyer Guido
• Co-promoter: Jordanova Albena
• Co-promoter: Rademakers Rosa
• Co-promoter: Timmerman Vincent
• Co-promoter: Timmermans Jean-Pierre
• Co-promoter: Vissenberg Kris
• Co-promoter: Weckhuysen Sarah

Research team(s)

• Laboratory of cell biology and histology

Project type(s)

• Research Project

Abstract

New drug candidates often have off-target effects resulting in adverse events, thus representing a major limitation for drug R&D. Safety Pharmacology (SP) aims to detect, understand and reduce undesirable pharmacodynamic effects early-on. Especially, cardiovascular (CV) toxicity is problematic, as it is the most prevalent reason for failure during preclinical development. Moreover, CV toxicity remains a key reason for drug attrition during clinical development and beyond. This indicates current SP screens fail to detect a number of (late-onset) functional or structural CV toxicities. Additionally, SP uses a significant number of laboratory animals, thereby creating opportunities for a better implementation of the 3Rs. The vision of INSPIRE is to advance and "inspire" SP by exploring new technological capabilities (WP1), addressing emerging CV concerns (WP2) and delivering new validated solutions for CV safety screening (WP3). To this end, INSPIRE unites expertise from academic teams, technology-providers, pharmaceutical companies, regulators and hospitals to create a European training platform for 15 Early Stage Researchers (ESRs). Key innovative aspects of INSPIRE include: i) in vitro humanized cardiomyocytes assays, ii) unparalleled in vivo hardware/software solutions, iii) in silico predictions of haemodynamics, iv) mass spectroscopy imaging of drug exposure, v) exploration of mechanisms of late-onset CV toxicity, as observed in cardio-oncology, and vi) early integration of feedback from industry and regulators. Overall, INSPIRE constitutes a multidisciplinary and intersectoral training programme (WP4) with a balanced combination of hands-on research training, intersectoral secondments, local courses and network-wide events on scientific and transferable skills, enabling future R&I collaborations. Hence, INSPIRE will equip the future generation of SP scientists with a wide range of scientific knowledge and the ability to adapt to a dynamic ever-changing industry.

Researcher(s)

• Promoter: Guns Pieter-Jan
• Co-promoter: De Meyer Guido
• Co-promoter: Heidbuchel Hein
• Co-promoter: Martinet Wim
• Co-promoter: Segers Vincent
• Co-promoter: Van Craenenbroeck Emeline

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

Mitochondria are the driving force behind virtually all vital cellular processes, including cellular proliferation, differentiation, cell death and epigenetic regulation. Consequently, their dysfunction is intricately connected to altered metabolic states and disease progression. We aim at acquiring a Seahorse XFp Analyzer, which can directly measure mitochondrial respiration and glycolysis through Oxygen Consumption Rate (OCR) and Extracellular Acidification Rate (ECAR) in different biological samples. Determination of cellular metabolic phenotype and mitochondrial activity is crucial for precise characterization of the research models and the pathophysiological alterations studied in various research disciplines across the University of Antwerp; including reproductive biology and toxicology, cell biology, neurodegenerative disease, cardiovascular function, cancer, obesity, diabetes, metabolic disorders, immunology, virology and toxicology, amongst others. This is also a key for drug screening and development of new treatment strategies. Seahorse XF analyzers offer the most sensitive and accurate technology with the highest throughput compared to other alternatives. It has contributed to ground-breaking discoveries demonstrated in an increasing number of publications in different research fields about the critical role of metabolism in a wide variety of diseases. It has been successfully applied on various types of cells and tissues including mammalian gametes, primary cells, adherent and suspension cell lines, cells differentiated from induced pluripotent stem cells, isolated mitochondria, 3D cultures, Zebrafish and mammalian embryos, roundworms, fruit flies and yeast. Adding to the broad applicability of the platform, the XF technology employs a label-free, non-invasive methodology allowing samples to be used post-measurement for other investigations. The Seahorse XFp Analyzer will directly contribute to several ongoing and future research within laboratories belonging to different departments and faculties at UA. Furthermore, this new platform will not only facilitate our on-site accessibility, but will also increase our national and international competitiveness. It will further support multidisciplinary networking and collaboration and shall further increase our scientific research excellence.

Researcher(s)

• Promoter: Leroy Jo
• Co-promoter: De Meyer Guido
• Co-promoter: Knapen Dries
• Co-promoter: Timmerman Vincent

Research team(s)

• Veterinary physiology and biochemistry

Project type(s)

• Research Project

Abstract

Morphological studies indicate that the vast majority of dying cells in advanced human atherosclerotic plaques undergo necrosis. Although the role of necrosis in atherosclerosis remains ill-defined, a growing body of evidence suggests that necrotic death stimulates atherogenesis and plaque instability through induction of inflammation and enlargement of a central necrotic core. For a long time, necrosis has been considered as a merely accidental and uncontrolled form of cell death, but recent data suggest that it can also occur in a regulated fashion. Necroptosis is the best characterized form of regulated necrosis and requires receptor interacting protein kinases (RIPKs) as key regulators. However, other examples such as ferroptosis are also emerging. Because regulated necrosis is considered as an important research target to stabilize plaques, the following objectives are defined: (1) inhibition of necroptosis and ferroptosis in atherosclerosis using mice containing catalytically inactive RIPK1, or transgenic mice overexpressing the anti-ferroptosis enzyme GPX4, (2) stabilization of atherosclerotic plaques with potent and selective inhibitors targeting necroptosis or ferroptosis, and (3) identification of the molecular mechanisms modulating regulated necrosis in atherosclerosis. This project may lead to the discovery of novel anti atherosclerosis therapies, and will allow a significant advance in the fundamental understanding of regulated necrosis in atherosclerosis.

Researcher(s)

• Promoter: Martinet Wim
• Co-promoter: De Meyer Guido
• Fellow: Puylaert Pauline

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

Atherosclerosis is an inflammatory disease of the arterial wall leading to myocardial infarction, stroke and peripheral arterial disease. We published that elastin fragmentation, due to a mutation (C1039G+/-) in the fibrillin-1 (Fbn1) gene, promotes atherogenesis and a highly unstable plaque phenotype in apolipoprotein E deficient (ApoE-/-) mice on a Western diet. Interestingly, ApoE-/-Fbn1C1039G+/- mice reveal substantial intraplaque (IP) neovascularization, which is a typical feature of advanced human atherosclerotic plaques, but rarely observed in animal models. Because clinical evidence links IP angiogenesis with progressive and unstable vascular disease, we investigate whether inhibition of IP neovascularization has a beneficial effect on atherogenesis and plaque stability. Hitherto, blocking VEGF was the primary strategy to reduce neovascularization. Unfortunately, limited efficacy and adverse effects have downsized its success, even when multiple blockers were used simultaneously. In view of the above mentioned findings, we will investigate the following pharmacological approaches to inhibit IP angiogenesis and to stabilise atherosclerotic plaques: a nitric oxide (NO) donor (WP 1), glycolysis inhibitors (WP 2&3) and the olive polyphenol hydroxytyrosol (WP 4). WP 1 and 2 have already been performed in the framework of the Horizon 2020 MSCA-ITN project Moglynet, which started in May 2016. WP 3 and 4 will be finalised through the present DOCPRO 1. WP1: Because it has been shown that NO is an endogenous antiangiogenic mediator, we investigated the effect of the NO donor molsidomine on IP angiogenesis, atherogenesis and plaque stability in the ApoE-/-Fbn1C1039G+/- mouse model. We found that molsidomine favoured some features of atherosclerotic plaque stability and reduced myocardial infarction. However, the occurrence of IP neovascularization, the number of microvessels and the occurrence of haemorrhages in plaques were not affected (manuscript submitted). WP 2: Given that endothelial cells (ECs) rely on glycolysis for up to 85% of their energy demand, targeting the glycolytic pathway represents an attractive novel strategy to inhibit IP angiogenesis. Studies in the oncology field already showed that transient and partial inhibition of glycolysis in proliferating ECs inhibits pathological angiogenesis without interfering in the metabolism of healthy cells. In WP 2, we investigated the effects and the mechanism of action of glycolysis inhibitor 3PO [3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one]. We found that in atherosclerotic ApoE−/−Fbn1C1039G+/− mice 3PO (50 μg/g, i.p.) reduced IP neovascularization and haemorrhages by 50% in a preventive regimen and by 38% in a curative regimen. However, the reduction in IP microvessels did not exert a significant effect on plaque composition. Nevertheless, 3PO reduced plaque formation, indicating that 3PO already has an effect in the onset of atherosclerosis. We could demonstrate that 3PO does not bind to PFKFB3, a key regulating enzyme in glycolysis, but inhibits glycolysis indirectly by lowering the intracellular pH due to blockade of monocarboxylate transporter 4 (manuscript in preparation). WP 3: Subsequently, we initiated WP 3 in order to evaluate in vitro and in ApoE-/-Fbn1C1039G+/- mice the effect of compound AZ67, which is a very potent inhibitor of PFKFB3. These experiments are ongoing and will be finalised during the duration of the DOCPRO1 grant. WP 4: Because it has recently been shown that the olive polyphenol hydroxytyrosol can inhibit angiogenesis both ex vivo and in vivo, we will investigate in WP 4 the effects of hydroxytyrosol on IP angiogenesis, atherogenesis and plaque stability in ApoE-/- Fbn1C1039G+/- mice. We already obtained interesting preliminary in vitro data. Further in vitro and in vivo experiments will be carried out during the duration of the DOCPRO1 grant.

Researcher(s)

• Promoter: De Meyer Guido
• Fellow: Emini Besa

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice and one of the most common causes of stroke and heart failure. AF is induced by electrical, contractile, and structural remodeling of the atria. Moreover, AF itself induces these changes, leading to a vicious circle ("AF begets AF"). Tissue inflammation and fibrosis play an important role in the structural changes, and form the basis of subsequent electrical and contractile atrial dysfunction. Current therapy is limited to rhythm control using antiarrhythmic drugs, but these drugs do not target the structural problem. That may explain why they are only marginally effective. Ablation by electrical isolation of the pulmonary veins (PVI) has broadened the medical opportunities, but it is also unsatisfactory since it addresses only part of the atria. This explains the high relapse rate in patients with more widespread atrial disease (and more persistent forms of AF). More extensive ablations have not shown better results, as can be anticipated by the fact that more destruction will not solve a primarily structural problem. There is a clear medical need for a treatment targeting the underlying pathophysiology leading to structural atrial remodeling. In this project, we will test the hypothesis that the neuregulin-1 (NRG-1)/ErbB pathway is an inhibitory pathway in development of atrial fibrillation. NRG-1 is a member of the epidermal growth factor family that binds to tyrosine kinase receptors and has cell protective and regenerative properties in the heart during heart failure. We recently discovered that NRG-1 has anti-inflammatory and anti-fibrotic properties in different organs, including the heart. As mentioned, fibrosis and inflammation are the main features of structural atrial remodeling present in AF. We hypothesize that (1) the endothelium-derived NRG-1 – ErbB4 system is activated in atrial tissue of patients with atrial fibrillation. We will harvest atrial tissue samples during cardiac surgery procedures from patients with and without AF and determine expression of NRG-1 and its receptors by histology. We will determine (2) whether NRG-1 attenuates atrial fibrosis and atrial fibrillation in two mouse models of atrial fibrillation. For this aim we will use transgenic mouse models that spontaneously develop atrial fibrosis and AF. We will treat these mice with different doses of NRG-1, continuously monitor cardiac rhythm and function, and evaluate histological changes in atria after 4 weeks of treatment. We will (3) develop a sterile pericarditis large animal model of AF in pigs. We will fully characterize reprogramming of different atrial cell types by RNA sequencing. Finally, we will determine (4) whether NRG-1 attenuates atrial fibrosis and atrial fibrillation in these pigs. If successful, this project could open new avenues for treatment of atrial fibrillation by addressing atrial tissue remodeling.

Researcher(s)

• Promoter: Heidbuchel Hein
• Co-promoter: De Keulenaer Gilles
• Co-promoter: De Meyer Guido

Research team(s)

• Cardiovascular diseases (CARDIOVASC)

Project type(s)

• Research Project

Abstract

Necrosis is a type of cell death characterized by a gain in cell volume, swelling of organelles, rupture of the plasma membrane and subsequent loss of intracellular contents. For a long time, the process has been considered as a merely accidental and uncontrolled form of cell death, but accumulating evidence suggests that it can also occur in a regulated fashion. Necroptosis is the most understood form of regulated necrosis and requires receptor interacting protein (RIP) kinases as key regulators, but also other examples such as ferroptosis are emerging. Morphological studies using transmission electron microscopy indicate that the vast majority of dying cells in advanced human atherosclerotic plaques undergo necrosis. Although the role of necrosis in atherosclerosis remains ill-defined, a growing body of evidence suggests that necrotic death stimulates atherogenesis and plaque instability through induction of inflammation and enlargement of the necrotic core. Therefore, the following objectives are defined in the present research proposal: (1) Identification of potential beneficial effects of macrophage-specific RIP1 gene deletion on atherosclerosis development, and (2) stabilization of atherosclerotic plaques with potent and selective inhibitors targeting RIP1 kinase activity or ferroptosis. The project may contribute to the development of novel (add-on) therapies for stabilization of atherosclerotic plaques.

Researcher(s)

• Promoter: De Meyer Guido
• Co-promoter: Augustyns Koen
• Co-promoter: Martinet Wim
• Fellow: Coornaert Isabelle

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

Atherosclerotic plaque rupture is the leading cause of acute cardiovascular syndromes and is responsible for 3.9 million deaths in Europe every year. Preventive strategies are greatly needed to reduce the health care burden of cardiovascular disease (CVD). The Mediterranean diet results in a lower CVD risk, with virgin olive oil as its key element. Many of the health-promoting effects are ascribed to the olive polyphenols (OPs) and recently a link with autophagy induction was shown. Autophagy is a cellular housekeeping mechanism and autophagy deficiency is detrimental in the development of CVD. Thus, inducing autophagy is likely to be an effective preventive strategy. OPs were identified as natural autophagy inducers, but further research is needed to define the contribution of this mechanism to their atheroprotective effects. Therefore, we aim to elucidate the role of endothelial cell and vascular smooth muscle cell autophagy in the atheroprotective effects of OPs. The research objectives are divided in 3 work packages: (1) Selection of the most potent autophagy-inducing OP and the most therapeutically effective dose, (2) Investigation of the vasomotor effects of an OP and the role of autophagy and (3) Investigation of the atheroprotective effects of an OP and the role of autophagy. This project will give insight in the mechanism of action of OPs and is an important step towards the implementation of OP nutraceuticals for the prevention of cardiovascular disease.

Researcher(s)

• Promoter: De Meyer Guido
• Co-promoter: Martinet Wim
• Fellow: Roth Lynn

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

The requested infrastructure (comprehensive liquid chromatograph-ion mobility-quadrupole time of flight mass spectrometer LCxLC-IM-QTOFMS) combines several state-of-the-art technologies into one platform which aims at bringing metabolomics research to the next level. As such, the infrastructure will deliver a combined five-dimension separation and detection technology, the first of its kind in Belgium. This instrument will be dedicated to metabolomics research, the science of endogenous metabolites in cells, tissues or organisms. The infrastructure will be able to optimally separate, detect and identify the very broad and complex chemical space of metabolites ranging from very polar (e.g. amino acids) to non-polar (e.g. lipids and hormones) at low nanomolar concentration range. Within UA, there is a growing need to combine the currently scattered efforts in metabolomics, an Emerging Frontline Research Domain in the UA research scene. Research ranges from drug discovery (mode of action and pharmacokinetic profiling), biomarker and toxicity studies to advanced data-analysis and systems biology approaches, but a dedicated metabolomics infrastructure to strengthen these studies is currently missing. As such, the investment in a core facility together with the gathering of nine research groups from five departments and two faculties would centralize the metabolomics research. This will position UA as a key player in the academic metabolomics research in the BeNeLux and worldwide.

Researcher(s)

• Promoter: Covaci Adrian
• Co-promoter: Augustyns Koen
• Co-promoter: Baggerman Geert
• Co-promoter: Bervoets Lieven
• Co-promoter: De Meester Ingrid
• Co-promoter: De Meyer Guido
• Co-promoter: Hermans Nina
• Co-promoter: Laukens Kris
• Co-promoter: Lemière Filip
• Co-promoter: Maes Louis
• Co-promoter: van Nuijs Alexander

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

Aging affects the whole body and is linked with metabolic dysfunction, loss of cellular stress resistance and accumulation of cellular damage. Aging is one of the strongest risk factors for the development of both vascular stiffening and neurodegenerative diseases such as Alzheimer's disease (AD). Many of the pathologies linked to aging are now recognized as being highly characteristic of neurodegenerative diseases – suggesting that both vascular stiffening and AD progression may be interconnected via molecular aging pathologies. Protracted, highly complex processes such as aging require the coherent coordination of many different physiological processes. To orchestrate such complex events the body uses proteins termed 'hubs' that can control a multiplicity of physiological processes simultaneously. Our laboratory has already identified multiple 'hubs' within somatic aging networks and in this context we shall specifically investigate, using advanced informatics technologies, how certain key proteins may interconnect these two pathologies. The functional activity of such 'hub' proteins may represent an important target to study for aging, vascular and neurodegenerative research. We propose that the identification of the key age-dependent controlling factors, common between vascular stiffening and AD processes will reveal multiple important targets for future investigation and eventual therapeutic strategy design.

Researcher(s)

• Promoter: Maudsley Stuart
• Co-promoter: De Meyer Guido
• Fellow: Hendrickx Jhana

Research team(s)

Project type(s)

• Research Project

Abstract

Proposed by the University, the Francqui Foundation each year awards two Francqui Chairs at the UAntwerp. These are intended to enable the invitation of a professor from another Belgian University or from abroad for a series of ten lessons. The Francqui Foundation pays the fee for these ten lessons directly to the holder of a Francqui Chair.

Researcher(s)

• Promoter: De Meyer Guido

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

The elasticity of the arterial wall is a physiologically elegant solution of nature for smoothing the pulsatile flow of blood from the heart to peripheral tissues. The loss of this elasticity during life is a consequence of pathophysiological alterations in the vessels eventually causing arterial stiffening. Emerging evidence demonstrates that arterial stiffness is an important driving force for multiple heart, kidney and brain pathologies (end-organ damage). Nevertheless, it is currently not clear which molecular pathways contribute to arterial stiffness and whether similar mechanisms link diverse end-organ pathologies. Therefore, the present proposal aims to investigate the following research questions in three work packages: Work package 1: Pathophysiological characterization of two mouse models of arterial stiffening and its relationship with end-organ damage. In this part of the project, we will characterize mouse models of two pathophysiological processes leading to arterial stiffness: endothelial dysfunction and extracellular matrix modification/calcification. Two appropriate mouse models, i.e. eNOS knockout mice and warfarin exposed mice will be examined in a longitudinal manner to investigate the time-dependent development of arterial stiffness and its relationship with end-organ damage (heart and kidney damage and brain degeneration). In a next step, a combined mouse model of arterial stiffness and cerebral beta-amyloid accumulation (cross breeding of one of the above models with APP23 transgenic mice) will be applied to explore whether arterial stiffness is able to enhance beta-amyloid accumulation in the brain, thereby promoting the development/progression of Alzheimer's disease. Techniques that will be used to measure arterial stiffness and end-organ damage include high-frequency ultrasound (Vevo2100), tonometry, pressure myography, immunohistochemistry and behavioral assessment of learning and cognition. Work package 2: What are the age-related molecular mechanisms that underlie arterial stiffness leading to end-organ damage? The second part of the project aims to unravel the (common) molecular pathway(s) that underlie the development of arterial stiffness and the end-organ damage by comparing protein expression/post-translational modification status in arteries, hearts, kidneys and brains originating from mice with and without arterial stiffening, using mass spectrometric isobaric mass-tag labeling proteomics (iTRAQ). We aim to investigate the age-dependent generation of potentially convergent pathological signaling processes, across the lifespan of mice, in stiffening arteries, damaged heart and kidney tissue and degenerating brain tissues. The search for potential common molecular pathway(s) ('disease signatures') underlying the development of arterial stiffness may allow the identification of new targets for the prevention or treatment of arterial stiffness and ensuing end-organ damage. Work package 3: How can arterial stiffness and subsequent end-organ damage be prevented or treated? The last work package will evaluate the efficacy of substances that potentially prevent or treat the development of arterial stiffness and the resulting end-organ damage, more in particular heart and kidney failure as well as beta-amyloid accumulation in the brain. Substances that will be tested include molecules that modulate new targets that were identified during the protein expression studies (WP2), affect endothelial dysfunction (NO-donor or guanylate cyclase activator), inhibit calcification (pyrophosphate) or stimulate autophagy (mTOR inhibitor). Taken together, this project aims to unravel the molecular processes involved in arterial stiffness that might lead to prevention and/or treatment of arterial stiffness and hence reduce the risk and severity of age-related heart and kidney damage and brain degeneration.

Researcher(s)

• Promoter: De Meyer Guido
• Co-promoter: D'Haese Patrick
• Co-promoter: Maudsley Stuart

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project website

Project type(s)

• Research Project

Abstract

Necrosis is a type of cell death characterized by a gain in cell volume, swelling of organelles, rupture of the plasma membrane and subsequent loss of intracellular contents. For a long time, the process has been considered as a merely accidental and uncontrolled form of cell death, but accumulating evidence suggests that it can also occur in a regulated fashion. Necroptosis is the most understood form of regulated necrosis and requires receptor interacting protein (RIP) kinases as key regulators, but also other examples such as ferroptosis are emerging. Morphological studies using transmission electron microscopy indicate that the vast majority of dying cells in advanced human atherosclerotic plaques undergo necrosis. Although the role of necrosis in atherosclerosis remains ill-defined, a growing body of evidence suggests that necrotic death stimulates atherogenesis and plaque instability through induction of inflammation and enlargement of the necrotic core. Therefore, the following objectives are defined in the present research proposal: (1) Identification of potential beneficial effects of macrophage-specific RIP1 gene deletion on atherosclerosis development, and (2) stabilization of atherosclerotic plaques with potent and selective inhibitors targeting RIP1 kinase activity or ferroptosis. The project may contribute to the development of novel (add-on) therapies for stabilization of atherosclerotic plaques.

Researcher(s)

• Promoter: De Meyer Guido
• Co-promoter: Augustyns Koen
• Co-promoter: Martinet Wim
• Fellow: Coornaert Isabelle

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

The application concerns an innovative microscopy platform for visualizing cells, tissue specimen and living small model organisms in three dimensions at unprecedented speed and with excellent resolution and contrast. As a unique feature, the platform is equipped with a light-sheet module, which is based on an orthogonal configuration of laser-generated, micrometer-thin plane illumination and sensitive one-shot detection. Seamless integration with confocal modalities enables imaging the same sample from the micro- to the mesoscale. The device has a broad application radius in the neurosciences domain inter alia for studying neurodegeneration and -regeneration (e.g. whole brain imaging, optogenetics); but it also has direct utility in various other fields such as cardiovascular research (e.g. plaque formation and stability), plant developmental research (e.g. protein localization during plant growth) and ecotoxicology (e.g. teratogenicity and developmental defects in zebrafish). Furthermore, its modular construction will enable adaptation and targeted expansion for future imaging needs.

Researcher(s)

• Promoter: Timmermans Jean-Pierre
• Co-promoter: Adriaensen Dirk
• Co-promoter: De Meyer Guido
• Co-promoter: De Vos Winnok
• Co-promoter: D'Haese Patrick
• Co-promoter: Giugliano Michele
• Co-promoter: Jordanova Albena
• Co-promoter: Keliris Georgios A.
• Co-promoter: Knapen Dries
• Co-promoter: Maudsley Stuart
• Co-promoter: Ponsaerts Peter
• Co-promoter: Timmerman Vincent
• Co-promoter: Vissenberg Kris

Research team(s)

• Laboratory of cell biology and histology

Project type(s)

• Research Project

Abstract

Despite recent scientific and technological advances, cardiovascular disease remains the leading cause of morbididy and mortality worldwide. Autophagy, a subcellular process for bulk destruction of proteins and organelles in lysosomes, has been implicated in the pathogenesis of atherosclerosis and a wide range of heart pathologies. However, the precise role of autophagy in these contexts remains obscure. In addition, the physiological significance of autophagy in the normal vasculature is largely unknown. Therefore, the following objectives are defined in the present research proposal: (1) study of the effect of autophagy deficiency in smooth muscle cells or endothelial cells on vasomotor function and blood pressure, (2) study of the effect of autophagy deficiency on the progression and stability of atherosclerotic plaques, and (3) prevention of atherosclerotic plaque rupture and downstream complications such as myocardial infarction and sudden death through pharmacological induction of autophagy. This project will give insight whether autophagy is beneficial or detrimental for cardiovascular disease and whether it plays a role in normal vascular function.

Researcher(s)

• Promoter: Martinet Wim
• Co-promoter: De Meyer Guido

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

Despite recent scientific and technological advances, cardiovascular disease remains the leading cause of morbididy and mortality worldwide. Autophagy, a subcellular process for bulk destruction of proteins and organelles in lysosomes, has been implicated in the pathogenesis of atherosclerosis and a wide range of heart pathologies. However, the precise role of autophagy in these contexts remains obscure. In addition, the physiological significance of autophagy in the normal vasculature is largely unknown. Therefore, the following objectives are defined in the present research proposal: (1) study of the effect of autophagy deficiency in smooth muscle cells or endothelial cells on vasomotor function and blood pressure, (2) study of the effect of autophagy deficiency on the progression and stability of atherosclerotic plaques, and (3) prevention of atherosclerotic plaque rupture and downstream complications such as myocardial infarction and sudden death through pharmacological induction of autophagy. This project will give insight whether autophagy is beneficial or detrimental for cardiovascular disease and whether it plays a role in normal vascular function.

Researcher(s)

• Promoter: Martinet Wim
• Co-promoter: De Meyer Guido
• Fellow: De Munck Dorien

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

Necrosis is a type of cell death characterized by a gain in cell volume, swelling of organelles, rupture of the plasma membrane and subsequent loss of intracellular contents. For a long time, the process has been considered as a merely accidental and uncontrolled form of cell death, but accumulating evidence suggests that it can also occur in a regulated fashion. Necroptosis is the most understood form of regulated necrosis and requires receptor interacting protein (RIP) kinases as key regulators, but also other examples such as ferroptosis are emerging. Morphological studies using transmission electron microscopy indicate that the vast majority of dying cells in advanced human atherosclerotic plaques undergo necrosis. Although the role of necrosis in atherosclerosis remains ill-defined, a growing body of evidence suggests that necrotic death stimulates atherogenesis and plaque instability through induction of inflammation and enlargement of the necrotic core. Therefore, the following objectives are defined in the present research proposal: (1) Identification of potential beneficial effects of macrophage-specific RIP1 gene deletion on atherosclerosis development, and (2) stabilization of atherosclerotic plaques with potent and selective inhibitors targeting RIP1 kinase activity or ferroptosis. The project may contribute to the development of novel (add-on) therapies for stabilization of atherosclerotic plaques.

Researcher(s)

• Promoter: Martinet Wim
• Co-promoter: Augustyns Koen
• Co-promoter: De Meyer Guido
• Fellow: Coornaert Isabelle

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

Despite recent scientific and technological advances, cardiovascular disease remains the leading cause of morbididy and mortality worldwide. Autophagy, a subcellular process for bulk destruction of proteins and organelles in lysosomes, has been implicated in the pathogenesis of atherosclerosis and a wide range of heart pathologies. However, the precise role of autophagy in these contexts remains obscure. In addition, the physiological significance of autophagy in the normal vasculature is largely unknown. Therefore, the following objectives are defined in the present research proposal: (1) study of the effect of autophagy deficiency in smooth muscle cells or endothelial cells on vasomotor function and blood pressure, (2) study of the effect of autophagy deficiency on the progression and stability of atherosclerotic plaques, and (3) prevention of atherosclerotic plaque rupture and downstream complications such as myocardial infarction and sudden death through pharmacological induction of autophagy. This project will give insight whether autophagy is beneficial or detrimental for cardiovascular disease and whether it plays a role in normal vascular function.

Researcher(s)

• Promoter: Martinet Wim
• Co-promoter: De Meyer Guido
• Fellow: De Munck Dorien

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

The mission of MoGlyNet is to define a joint doctorate educational training model in Drug Discovery and Development where Academia and Industry join their forces for:- creating a common platform of knowledge and language for early stage researchers (ESR) working in the Drug Discovery and Development area aiming to convey complementary pharma-skills- exploiting this platform to train a new generation of cutting-edge researchers and professionals highly attractive for employment by the European Pharma-industry- establishing structures for long-term cooperation, strengthening the relationships among the leading Universities and Pharma-enterprises and to continuously develop the research training platform that European industry relies on.

Researcher(s)

• Promoter: De Meyer Guido
• Co-promoter: Martinet Wim

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

The Infla-Med consortium performs fundamental research on the pathophysiological processes of inflammatory diseases (cardiovascular, gastrointestinal, renal and infectious disease) by using a multidisciplinary approach (pathophysiology, pharmacology, biochemistry and medicinal chemistry). The consortium is embedded within the research priorities 'Drug Research' and 'Infectious Diseases' of the University of Antwerp. Recently, the University of Antwerp assigned the Infla-Med consortium as Research Consortium of Excellence.

Researcher(s)

• Promoter: De Meyer Guido
• Co-promoter: Augustyns Koen
• Co-promoter: De Meester Ingrid
• Co-promoter: De Winter Benedicte
• Co-promoter: D'Haese Patrick
• Co-promoter: Lambeir Anne-Marie
• Co-promoter: Maes Louis
• Co-promoter: Vrints Christiaan

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand the Hercules Foundation. UA provides the Hercules Foundation research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: De Meyer Guido
• Co-promoter: Claeys Marc
• Co-promoter: De Keulenaer Gilles
• Co-promoter: D'Haese Patrick
• Co-promoter: Loeys Bart
• Co-promoter: Vrints Christiaan

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand the Hercules Foundation. UA provides the Hercules Foundation research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Maes Louis
• Co-promoter: Delputte Peter
• Co-promoter: De Meyer Guido
• Co-promoter: Dewilde Sylvia
• Co-promoter: Kumar-Singh Samir
• Co-promoter: Lambeir Anne-Marie
• Co-promoter: Lebeer Sarah
• Co-promoter: Leroy Jo
• Co-promoter: Van Cruchten Steven
• Co-promoter: Wenseleers Wim

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand IFEB. UA provides IFEB research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Van Hal Guido
• Co-promoter: Beutels Philippe
• Co-promoter: De Loof Hans
• Co-promoter: De Meyer Guido

Research team(s)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand the client. UA provides the client research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: De Meyer Guido

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

Autophagy is a reparative, life-sustaining process that has been associated with a plethora of different pathological conditions. Although some histological studies have demonstrated that autophagy occurs in advanced atherosclerotic plaques, the role of autophagy in atherogenesis, plaque stability and vasomotor function is largely unknown. In the present research proposal, we aim to perform a detailed investigation of the role of autophagy in atherosclerosis and in normal vascular function.

Researcher(s)

• Promoter: Martinet Wim
• Co-promoter: De Meyer Guido

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

This project represents a research contract awarded by the University of Antwerp. The supervisor provides the Antwerp University research mentioned in the title of the project under the conditions stipulated by the university.

Researcher(s)

• Promoter: De Meyer Guido

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

Rupture of atherosclerotic plaques remains the main cause of acute cardiovascular syndromes and death. The need for novel plaque stabilising therapies is high, but adequate animal models are lacking. We recently discovered that ApoE-/- mice with a disturbed fibrillin production (ApoE-/-/C1039G+/- mice) fed a Western-type diet develop more unstable plaques as compared to ApoE-/- mice. Interestingly, acute plaque rupture and death occurred very frequently: 50% of the ApoE-/-/C1039G+/- mice died suddenly within 20 to 52 weeks, most likely due to cerebral embolism, whereas all ApoE-/- mice survived. Further optimisation and characterisation of this model could provide better insights in the mechanisms of plaque rupture, and also give for the first time the opportunity to evaluate potential plaque stabilising therapies on genuine clinical end points of plaque rupture (embolism, stroke and/or death) in mice. The aims of the project are: 1) Further optimisation and characterisation of the model. We will investigate whether additional destabilising stimuli can augment and speed up the incidence of plaque rupture, which is important for the evaluation of plaque stabilising therapies. 2) Validation of this model with established plaque stabilising drugs such as statins. 3) Study of the effects of novel potential plaque stabilising therapies (phytosterols, NO-donor).

Researcher(s)

• Promoter: De Meyer Guido
• Co-promoter: Martinet Wim
• Fellow: Roth Lynn

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

In this project, we aim to perform a detailed investigation of the role of autophagy in atherosclerosis and in normal vascular function: (1) Study of the effect of pharmacological induction of autophagy on atherogenesis and plaque stability (molecular pathways of autophagy induction, effect on plaque formation and composition), (2) Study of the effect of autophagy deficiency on the progression and stability of atherosclerotic plaques, (3) Study of the effect of autophagy deficiency or induction on vasomotor function. This project will give insight whether autophagy is beneficial or detrimental for the development and stability of atherosclerotic plaques and whether it plays a role in normal vascular function.

Researcher(s)

• Promoter: De Meyer Guido
• Co-promoter: Martinet Wim

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

The first aim of this project is to obtain better insight into the pro-inflammatory responses that might occur after druginduced macrophage death in atherosclerotic plaques. A second aim is to prevent or inhibit enlargement of the necrotic core by crossbreeding RIP3-/- mice, deficient in necrotic signaling, with atherosclerosis-prone apoE-/- mice. Alternatively, necrosis will be inhibited via administration of necrosis inhibitors, both in vitro and in vivo. Overall, the project may contribute to a more purposeful treatment of unstable plaques.

Researcher(s)

• Promoter: Martinet Wim
• Co-promoter: De Meyer Guido

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

This project represents a research agreement between the UA and on the onther hand IWT. UA provides IWT research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: De Meyer Guido
• Co-promoter: Martinet Wim
• Fellow: Van der Donckt Carole

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

In this study, we will investigate the role of autophagy (a cell survival and death pathway) and adiponectin (an endogenous hormone produced by fat cells) in a protective post-myocardial infarction reperfusion therapy called postconditioning. Adiponectin has protective myocardial effects that limit lethal reperfusion injury. However, patients with central obesity have low plasma levels of adiponectin, which may confound the cardioprotective properties of postconditioning.

Researcher(s)

• Promoter: Vrints Christiaan
• Co-promoter: Claeys Marc
• Co-promoter: De Meyer Guido
• Co-promoter: Martinet Wim
• Co-promoter: Timmermans Jean-Pierre

Research team(s)

Project type(s)

• Research Project

Abstract

This proposal aims at developing inhibitors of cysteine protease Atg4B, a prime regulator of autophagy, as innovative tools for selective autophagy blocking. Additionally, inhibitor-derived probe molecules will be prepared, enabling further study of Atg4B's role in cellular physiology and in the initiation and propagation of autophagic processes.

Researcher(s)

• Promoter: Van Der Veken Pieter
• Co-promoter: Augustyns Koen
• Co-promoter: De Meyer Guido
• Co-promoter: Martinet Wim

Research team(s)

• Medicinal Chemistry (UAMC)

Project type(s)

• Research Project

Abstract

The aims of the project are: 1) Further optimisation and characterisation of the model. We will investigate whether additional destabilising stimuli can augment and speed up the incidence of plaque rupture, which is important for the evaluation of plaque stabilising therapies. 2) Validation of this model with established plaque stabilising drugs such as statins. 3) Study of the effects of novel potential plaque stabilising therapies (phytosterols, NO-donor).

Researcher(s)

• Promoter: De Meyer Guido
• Co-promoter: Bult Hidde
• Co-promoter: Martinet Wim
• Co-promoter: Verhoye Marleen

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

This project represents a research agreement between the UA and on the onther hand IWT. UA provides IWT research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: De Meyer Guido
• Co-promoter: Martinet Wim
• Fellow: Michiels Cédéric

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

Rupture of atherosclerotic plaques remains the main cause of acute cardiovascular syndromes and death. The need for novel plaque stabilising therapies is high, but adequate animal models are lacking. We recently discovered that ApoE-/- mice with a disturbed fibrillin production (ApoE-/-/C1039G+/- mice) fed a Western-type diet develop more unstable plaques as compared to ApoE-/- mice. Interestingly, acute plaque rupture and death occurred very frequently: 50% of the ApoE-/-/C1039G+/- mice died suddenly within 20 to 52 weeks, most likely due to cerebral embolism, whereas all ApoE-/- mice survived. Further optimisation and characterisation of this model could provide better insights in the mechanisms of plaque rupture, and also give for the first time the opportunity to evaluate potential plaque stabilising therapies on genuine clinical end points of plaque rupture (embolism, stroke and/or death) in mice. The aims of the project are: 1) Further optimisation and characterisation of the model. We will investigate whether additional destabilising stimuli can augment and speed up the incidence of plaque rupture, which is important for the evaluation of plaque stabilising therapies. 2) Validation of this model with established plaque stabilising drugs such as statins. 3) Study of the effects of novel potential plaque stabilising therapies (phytosterols, NO-donor).

Researcher(s)

• Promoter: De Meyer Guido
• Co-promoter: Martinet Wim
• Fellow: Roth Lynn

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

This project represents a research agreement between the UA and on the onther hand IWT. UA provides IWT research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: De Meyer Guido
• Co-promoter: Martinet Wim
• Fellow: Van der Donckt Carole

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

A growing body of evidence gathered in the research unit of Pharmacology at the University of Antwerp suggests that autophagy occurs in advanced atherosclerotic plaques. Despite the increasing knowledge on autophagy, its role in atherosclerosis remains poorly understood. The aim of this project is to study the role of cell-specific autophagy (macrophages versus smooth muscle cells) on the stability of atherosclerotic plaques in mice.

Researcher(s)

• Promoter: De Meyer Guido
• Fellow: Schrijvers Dorien

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

Rupture of unstable atherosclerotic plaques can lead to important atherothrombotic complications, such as myocardial infarction. Therefore, stabilisation of plaques is an important pharmacological target. In the destabilisation process macrophages play a key role, whereas smooth muscle cells contribute to plaque stability. The first aim of this project is to selectively induce autophagy of macrophages in atherosclerotic plaques by means of drugs. The second aim is to study the implications and possible complications of induction of macrophage autophagy in atherosclerotic plaques and the comparison with induction of other types of cell death (apoptosis, necrosis). In the third aim, we will investigate new drug targets that can affect cell death of macrophages. In the fourth aim we wish to develop drug eluting stents to induce selective induction of macrophage cell death in atherosclerotic plaques.

Researcher(s)

• Promoter: De Meyer Guido
• Co-promoter: Martinet Wim
• Fellow: De Meyer Inge

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

This project represents a research contract awarded by the University of Antwerp. The supervisor provides the Antwerp University research mentioned in the title of the project under the conditions stipulated by the university.

Researcher(s)

• Promoter: Timmermans Jean-Pierre
• Co-promoter: De Groote Chantal
• Co-promoter: De Meyer Guido
• Co-promoter: Timmerman Vincent
• Co-promoter: Van Marck Eric
• Co-promoter: Verbelen Jean-Pierre

Research team(s)

• Laboratory of cell biology and histology

Project type(s)

• Research Project

Abstract

Macrophages play a central role in atherosclerotic plaque destabilization, leading to acute coronary syndromes and sudden death. Removal of macrophages from plaques via pharmacological therapy may therefore represent a promising approach to stabilise vulnerable, rupture-prone lesions. In this project, we will evaluate strategies and unravel the mechanisms to deplete macrophages in atherosclerotic plaques via drug-induced cell death without affecting smooth muscle cell content.

Researcher(s)

• Promoter: De Meyer Guido
• Co-promoter: Martinet Wim

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

In this project, we would like to develop additional strategies for selective clearance of macrophages in atherosclerotic plaques. Furthermore, the influence of macrophage cdl death on the stability of plaques will be investigated. It should be noted that selective clearance of macrophages in plaques is a new concept in cardiovascular research that may contribute to a more purposeful treatment of unstable plaques.

Researcher(s)

• Promoter: De Meyer Guido
• Co-promoter: Martinet Wim

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: Herman Arnold
• Co-promoter: De Meyer Guido
• Co-promoter: Vrints Christiaan
• Fellow: Van Herck Jozef

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

Rupture of unstable atherosclerotic plaques can lead to important atherothrombotic complications, such as myocardial infarction. Therefore, stabilisation of plaques is an important pharmacological target. In the destabilisation process macrophages play a key role, whereas smooth muscle cells contribute to plaque stability. The first aim of this project is to selectively induce autophagy of macrophages in atherosclerotic plaques by means of drugs. The second aim is to study the implications and possible complications of induction of macrophage autophagy in atherosclerotic plaques and the comparison with induction of other types of cell death (apoptosis, necrosis). In the third aim, we will investigate new drug targets that can affect cell death of macrophages. In the fourth aim we wish to develop drug eluting stents to induce selective induction of macrophage cell death in atherosclerotic plaques.

Researcher(s)

• Promoter: De Meyer Guido
• Co-promoter: Martinet Wim
• Fellow: De Meyer Inge

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: De Keulenaer Gilles
• Promoter: De Meyer Guido

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

Macrophages play a central role in atherosclerotic plaque destabilization, leading to infarctions. The aim of the present research project is to investigate whether protein translation inhibitors can selectively clear macrophages from atherosclerotic plaques by induction of cell death of macrophages, but not of smooth muscle cells. The effect of the protein translation inhibitors on cell death of macrophages will be investigated on 3 levels: (1) cultured macrophages and smooth muscle cells; (2) explants of the rabbit carotid artery with atherosclerotic plaques; (3) local administration of a protein translation inhibitor to an atherosclerotic plaque via an osmotic minipump.

Researcher(s)

• Promoter: De Meyer Guido

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

The availability of a fast and adequate animal model of unstable plaques, including the induction of plaque microvessels, may lead to a better understanding of the pathophysiological mechanisms of plaque instability and rupture and may constitute the foundation of pharmacotherapy of unstable plaques. In this project, we will investigate whether microvessels can be induced in experimental atherosclerotic plaques and whether the affect growth, composition and stability of plaques. Furthermore, the effect of drugs on microvessels and plaque stability will be studied.

Researcher(s)

• Promoter: De Meyer Guido
• Co-promoter: Martinet Wim

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

In this study, microvessels will be induced in atherosclerotic plaques from rabbits. The influence of microvessels on growth, composition and stability of the plaque will be determined. On the other hand, the effect of pharmaca (statins, nitrogen monoxide donors) on microvessel development and plaque stability will be examined. In parallel, we also aim to get a better insight into the pathophysiological mechanisms underlying plaque instability and rupture as well as the development and validation of new endpoints for the evaluation of plaque stability.

Researcher(s)

• Promoter: Martinet Wim
• Co-promoter: De Meyer Guido

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

The study of atherosclerotic plaque stabilization is hampered by the lack of a good animal model. To develop a model for unstable atherosclerotic plaques, we will study substances that may promote transition from stable to unstable plaques.

Researcher(s)

• Promoter: De Meyer Guido

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

The endothelium plays an important role in the cardiovascular system. Due to its position between blood and myocytes of heart and vessels, it acts as a sensor of signals from the blood, which it transfers to the myocytes. As such, both types of endothelium in heart, the endocardial endothelium (EE) and the vascular endothelium (VE) of the myocardial capillaries, exert an important regulatory and protective influence on the heart muscle. Previous studies in VE showed that hemodynamic stress influences the expression of several genes. However, as VE and EE differ significantly with respect to structure, function and localisation, the influence on gene expression and the resulting effect on heart function are also likely to be very different. This study focuses on the influence of hemodynamic signals from the blood on gene expression in EE and cardiomyocytes. Both cell types will be submitted to different types of hemodynamic stress (pressure, flow, stretch). The expression of specific genes in these cells will be studied by quantitative RT-PCR, and the results will be correlated with the electrophysiological properties of the cells and with the performance of the isolated heart muscle. Second, the use of DNA arrays will yield a general image of gene expression. Depending on the results of these arrays, the function in heart of genes with an altered expression will be studied using classic molecular biological or electrophysiological techniques. The results of this study will significantly contribute to the insight in the influence of hemodynamic stress (blood pressure, heart rate) on heart muscle performance, especially concerning the role of the EE.

Researcher(s)

• Promoter: Herman Arnold
• Co-promoter: De Meyer Guido

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

In this project we will investigate the role of ß-amyloid peptide (Aß) and its precursor (APP) in atherosclerosis. Hitherto, APP has only been studied in brain tissue in Alzheimer's disease. A possible source for APP in atherosclerotic plaques are platelets. We will study 1) the localisation and distribution of APP and A? in human atherosclerotic plaques and in a model of atherosclerosis; 2) the association with inducible nitric oxide synthase (iNOS); 3) the influence of cholesterol and lipids on ?-amyloid deposition in models with APP overexpression; 4) the interaction between APP processing and iNOS expression; 5) the effect of Aß on the endothelial cell function of blood vessels. These data could lead to a better understanding of the role of processing of APP, derived from platelets, in the destabilisation and rupture of an atherosclerotic plaque and on the endothelial cell function of blood vessels.

Researcher(s)

• Promoter: De Meyer Guido
• Co-promoter: Martinet Wim
• Fellow: Jans Dominique

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

We plan to investigate the role of f3-amyloid peptide and its precursor (APP) in atherosclerosis. Hitherto, APP has only been studied in brain tissue in Alzheimer's disease. A possible source for APP in atherosclerotic plaques are platelets. This project may lead to a better understanding of the role of APP processing in the rupture of an atherosclerotic plaque and on the endothelial cell function of blood vessels.

Researcher(s)

• Promoter: De Meyer Guido
• Co-promoter: Herman Arnold
• Co-promoter: Kockx Mark

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

In this project we will investigate the role of ß-amyloid peptide (Aß) and its precursor (APP) in atherosclerosis. Hitherto, APP has only been studied in brain tissue in Alzheimer's disease. A possible source for APP in atherosclerotic plaques are platelets. We will study 1) the localisation and distribution of APP and A? in human atherosclerotic plaques and in a model of atherosclerosis; 2) the association with inducible nitric oxide synthase (iNOS); 3) the influence of cholesterol and lipids on ?-amyloid deposition in models with APP overexpression; 4) the interaction between APP processing and iNOS expression; 5) the effect of Aß on the endothelial cell function of blood vessels. These data could lead to a better understanding of the role of processing of APP, derived from platelets, in the destabilisation and rupture of an atherosclerotic plaque and on the endothelial cell function of blood vessels.

Researcher(s)

• Promoter: De Meyer Guido
• Co-promoter: Bult Hidde
• Co-promoter: Herman Arnold
• Co-promoter: Kockx Mark

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

Intimal thickening is a fertile soil for atherogenesis. The positioning of a soft silicone collar around the rabbit carotid artery induces intimal thickening within 14 days. The collar model has the great advantage that substances can be administered locally at the level of the vessel wall (in the collar), which strongly reduces the possibility of systemic adverse effects. On one hand the atherogenic potential of various compounds will be investigated. On the other hand strategies that may decrease intimal thickening or atherosclerosis, e.g. antisense strategies or gene transfer, will be studied.

Researcher(s)

• Promoter: De Meyer Guido
• Fellow: De Meyer Guido

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

In this project we will investigate the role of ß-amyloid peptide (Aß) and its precursor (APP) in atherosclerosis. Hitherto, APP has only been studied in brain tissue in Alzheimer's disease. A possible source for APP in atherosclerotic plaques are platelets. We will study 1) the localisation and distribution of APP and A? in human atherosclerotic plaques and in a model of atherosclerosis; 2) the association with inducible nitric oxide synthase (iNOS); 3) the influence of cholesterol and lipids on ?-amyloid deposition in models with APP overexpression; 4) the interaction between APP processing and iNOS expression; 5) the effect of Aß on the endothelial cell function of blood vessels. These data could lead to a better understanding of the role of processing of APP, derived from platelets, in the destabilisation and rupture of an atherosclerotic plaque and on the endothelial cell function of blood vessels.

Researcher(s)

• Promoter: De Meyer Guido
• Fellow: Jans Dominique

Research team(s)

Project type(s)

• Research Project

Abstract

An early and essential step in atherogenesis is the formation of intimal thickening. It is a site of predilection for the development of atherosclerotic plaques. The aim of this project is to perform quantitative RT-PCR of the mRNA of gene products that are involved in intimal thickening and atherosclerosis, such as serotonin receptors, pro- and anti-apoptotic proteins, endothelial and inducible nitric oxide synthase (eNOS and iNOS) and von Willebrand factor. In addition, we need a fast PCR technique to control the genetic background of knockout mice, such as Apo E-/- en iNOS-/-.

Researcher(s)

• Promoter: De Meyer Guido

Research team(s)

Project type(s)

• Research Project

Abstract

During atherosclerosis thickening of the vessel wall and accumulation of lipide, such as cholesterol, occur. Progressively this will lead to an atherosclerotic plaque. The lipid rich zone in the plaque remains separated from the blood by a fibreus cap. When this cap is thick, containing many smooth muscle cells, the plaque can be considered as stable. This means that the cap is unlikely to tear. On the other hand plaques may have a thin fibreus cap. The loss of smooth muscle cells by cell death (apoptosis) and consequently the production of fibreus tissue by these cells can destabilise the plaque, reading to an increased risk of tearing and a life-threatening situation. In this project we will investigate (1) the mechanism of the destabilisation, (2) whether an inflammatoly reaction can destabilise the plaques, (3) which cells are important in this inflammatory reaction, (4) whether we can influence this inflammatory reaction by anti-inflammatory drugs and in this way stabilise the plaque.

Researcher(s)

• Promoter: De Meyer Guido
• Co-promoter: Bult Hidde
• Co-promoter: Kockx Mark

Research team(s)

Project type(s)

• Research Project

Abstract

Placing a collar around the rabbit carotid artery induces intimal thickening. The role of inducible nitric oxide synthase in the migration and proliferation of smooth muscle cells, and the progression of an intimal thickening to an atheromatous lesion will be studied

Researcher(s)

• Promoter: De Meyer Guido

Research team(s)

Project type(s)

• Research Project

Abstract

Intimal thickening is a fertile soil for atherogenesis. The positioning of a soft silicone collar around the rabbit carotid artery induces intimal thickening within 14 days. The collar model has the great advantage that substances can be administered locally at the level of the vessel wall (in the collar), which strongly reduces the possibility of systemic adverse effects. On one hand the atherogenic potential of various compounds will be investigated. On the other hand strategies that may decrease intimal thickening or atherosclerosis, e.g. antisense strategies or gene transfer, will be studied.

Researcher(s)

• Promoter: De Meyer Guido
• Fellow: De Meyer Guido

Research team(s)

Project type(s)

• Research Project

Abstract

Advanced glycosylation end products (AGEs) are formed after reaction of glucose with proteins. In this project we will investigate whether local vascular application of AGEs accelerates atherosclerosis, increases the expression of adhesion molecules, induces the infiltration of leukocytes in the vessel wall, and leads to changes in vascular reactivity. Moreover, we will study the influence of local treatment with anti-oxidants, superoxide dismutase, aminoguanidine and modulators of nitric oxide biosynthesis on the effect of AGEs.

Researcher(s)

• Promoter: Herman Arnold
• Co-promoter: Bult Hidde
• Co-promoter: De Meyer Guido

Research team(s)

Project type(s)

• Research Project

Abstract

We will investigate to which extent the infiltration of leucocytes (polymorphonuclear leucocytes, monocytes, lymphocytes) in the vessel wall can contribute to the formation of intimal thickening. We will study which adhesion molecules are involved in the infiltration of leucocytes, which cytokines can modulate this infiltration and intimal thickening and whether inhibition of the infiltration of leucocytes can affect the formation of intimal thickening.

Researcher(s)

• Promoter: De Meyer Guido

Research team(s)

Project type(s)

• Research Project

Abstract

The development of atherosclerotic lesions can be considered as a local inflammatory reaction in large vessels. The early stadium of atherosclerose is characterized by the development of an intima, mainly containing smooth muscle cells, collagen- and elastine fibres. In this project, the role of leucocytes (neutrophils, monocytes/macrophages and lymphocytes) in the development and progression of intimal thickening will be studied in the rabbit. The involvement of various adhesion molecules during leucocyte infiltration in the vessel wall and of different cytokines in the inftima formation will be investigated.

Researcher(s)

• Promoter: Herman Arnold
• Co-promoter: De Meyer Guido

Research team(s)

Project type(s)

• Research Project

Abstract

We will investigate to which extent the infiltration of leucocytes (polymorphonuclear leucocytes, monocytes, lymphocytes) in the vessel wall can contribute to the formation of intimal thickening. We will study which adhesion molecules are involved in the infiltration of leucocytes, which cytokines can modulate this infiltration and intimal thichening and whether inhibition of the infiltration of leucocytes can affect the formation of intimal thichening.

Researcher(s)

• Promoter: De Meyer Guido

Research team(s)

Project type(s)

• Research Project

Abstract

The positioning of a non-occlusive collar around the rabbit carotid artery induces within 1 week a neo-intima, an early and essential step in the development of atherosclerosis. The formation of a neo-intima is preceded by an infiltration of leukocytes in the vessel wall. Therefore, the contribution of white blood cells to the development of a neo-intima and the concomitant changes in vascular reactivity will be investigated.

Researcher(s)

• Promoter: Herman Arnold
• Fellow: De Meyer Guido

Research team(s)

Project type(s)

• Research Project

Abstract

The positioning of a non-occlusive collar around the rabbit carotid artery induces within 1 week a neo-intima, an early and essential step in the development of atherosclerosis. The formation of a neo-intima is preceded by an infiltration of leukocytes in the vessel wall. Therefore, the contribution of white blood cells to the development of a neo-intima and the concomitant changes in vascular reactivity will be investigated.

Researcher(s)

• Promoter: Herman Arnold
• Fellow: De Meyer Guido

Research team(s)

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: Herman Arnold
• Fellow: De Meyer Guido

Research team(s)

Project type(s)

• Research Project