Research team
When minerals turn bad: deciphering the role of calciprotein particles in cardiovascular ageing and disease.
Abstract
As the world's aged population grows considerably, a parallel increase in the incidence of cardiovascular disease (CVD) is expected. Therefore, further research to determine preventive strategies and their underlying molecular mechanisms is greatly needed in order to reduce the health care burden of CVD. The recent discovery of a possible role of calciprotein particles (CPPs), which are blood-borne protein-mineral complexes, as facilitators of CVD established a new and promising field of research. Indeed, CPPs have been associated with atherosclerosis and the incidence of cardiovascular complications such as myocardial infarction. However, insightful studies on the underlying mechanisms are lacking. Our preliminary data indicate that primary CPPs (CPP1) increase arterial stiffness and induce overall vascular cell dysfunction. Therefore, in this research project, we aim to address the role of CPP1 in CVD by unravelling its underlying mechanisms. In order to do so, we will investigate the effect of CPP1 on CVD-related signalling pathways in vascular cells (WP1), arterial stiffness and vascular calcification (WP2) as well as its role in the progression of atherosclerosis (WP3 & WP4). In conclusion, this research project aims to deepen our understanding of CPPs' impact, particularly CPP1, on the cardiovascular system, paving the way for innovative anti-ageing therapies and contributes to the development of targeted interventions for age-related cardiovascular diseases.Researcher(s)
- Promoter: Roth Lynn
- Co-promoter: Neutel Cédric
Research team(s)
Project type(s)
- Research Project
Breaking down vascular barriers: decoding the impact of calciprotein particles in cardiovascular disease.
Abstract
As the world's aged population grows considerably, a parallel increase in the incidence of cardiovascular disease (CVD) is expected. Therefore, further research to determine preventive strategies and their underlying molecular mechanisms is greatly needed in order to reduce the health care burden of CVD. The recent discovery of a possible role of calciprotein particles (CPPs), which are blood-borne protein-mineral complexes, as facilitators of CVD established a new and promising field of research. Indeed, CPPs have been associated with atherosclerosis and the incidence of cardiovascular complications such as myocardial infarction. However, insightful studies on the underlying mechanisms are lacking. Our preliminary data indicate that primary CPPs (CPP1) increase arterial stiffness and induce overall vascular cell dysfunction. Therefore, in this research project, we aim to address the role of CPP1 in CVD by unravelling its underlying mechanisms. In order to do so, we will investigate the effect of CPP1 on CVD-related signalling pathways in vascular cells (WP1), arterial stiffness and vascular calcification (WP2) as well as its role in the progression of atherosclerosis (WP3 & WP4). In conclusion, this research project aims to deepen our understanding of CPPs' impact, particularly CPP1, on the cardiovascular system, paving the way for innovative anti-ageing therapies and contributes to the development of targeted interventions for age-related cardiovascular diseases.Researcher(s)
- Promoter: Roth Lynn
- Co-promoter: Martinet Wim
- Fellow: Neutel Cédric
Research team(s)
Project type(s)
- Research Project
Pathophysiology of vascular ageing.
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)
Project type(s)
- Research Project
From hit to lead: inducing basal autophagy for treating cardiovascular diseases.
Abstract
Autophagy is a normal physiological process that maintains intracellular homeostasis by degrading unnecessary or dysfunctional cellular components in lysosomes. This way, autophagy supports cell survival in unfavourable conditions and represents a reparative and life-sustaining process. Impaired autophagy is increasingly recognized as a hallmark of aging and of multiple human pathological conditions, including cardiovascular disease. Moreover, impaired autophagy has been linked with increased arterial stiffness, an independent risk marker of cardiovascular disease. Therefore, inducing autophagy could be a game-changer in the treatment of cardiovascular disease. However the potential of autophagy inducing drugs has not been realized yet due to the absence of potent and selective tool compounds. The current proposal will start from a number of hits identified in a high-throughput screening and will further validate these lead candidates through a series of in vitro and in vivo studies focussing on vascular biology. Using geneticallyengineered mice with cell-type specific autophagy defect, the selectivity of the final lead compound will be demonstrated. Moreover, we aim to establish preclincal proof of concept of autophagy induction as therapeutic strategy for cardiovascular ageing and the development of atherosclerosis.Researcher(s)
- Promoter: Guns Pieter-Jan
- Co-promoter: Martinet Wim
- Fellow: Neutel Cédric
Research team(s)
Project type(s)
- Research Project
From hit to lead: inducing basal autophagy for treating cardiovascular disease.
Abstract
Autophagy is a normal physiological process that maintains intracellular homeostasis by degrading unnecessary or dysfunctional cellular components in lysosomes. This way, autophagy supports cell survival in unfavourable conditions and represents a reparative and life-sustaining process. Impaired autophagy is increasingly recognized as a hallmark of aging and of multiple human pathological conditions, including cardiovascular disease. Inducing autophagy could be a game-changer in the treatment of cardiovascular disease, but the potential of autophagy inducing drugs has not been realized yet due to the absence of potent and selective tool compounds. The current proposal will start from a number of hits identified in a high-throughput screening and will further validate these lead candidates through a series of in vitro and in vivo studies focussing on vascular biology.Researcher(s)
- Promoter: Guns Pieter-Jan
- Fellow: Neutel Cédric
Research team(s)
Project type(s)
- Research Project