Research team
Expertise
My research focusses primarily on understanding the mechanisms involved in cardiovascular disease, primarily in cancer survivors and the normal ageing process. For this purpose, we use a wide range of murine models in which cardiovascular function is evaluated in vivo with echocardipgraphy and ex vivo using in-house developed organ bath set-ups.
SERPINA3 in cardiovascular disease: friend or foe?
Abstract
Recently, we discovered upregulation of SERPINA3, or alpha-1-antichymotrypsin, in both mice and patients with doxorubicin-induced cardiovascular toxicity. Also other clinical studies have reported SERPINA3 to be associated with adverse cardiovascular outcome in recent years. However, despite its prognostic potential for cardiovascular disease (CVD), the role of SERPINA3 in cardiovascular pathology remains poorly understood, and it is unknown whether SERPINA3 is part of a coping or disease mechanism. As such, the current proposal aims to shed light on the role of SERPINA3 in cardiovascular pathology by pursuing a translational approach. In vivo studies combining in-house well-established murine models of cardiovascular toxicity and heart failure (HF) with a SERPINA3 knock-out mouse strain will provide unique insight into the (patho)physiological role of SERPINA3. Moreover, single-cell RNA sequencing on cardiac and aortic tissue, complemented by in vitro work, will identify the molecular pathways involving SERPINA3 and its cellular source. Finally, the preclinical findings will be validated in HF patients by assessing the association of serum SERPINA3 with functional and molecular data of an existing cohort of HF patients. Ultimately, this project will determine whether elevated SERPINA3 levels pose cardiovascular risk for patients and further validate its prognostic value as well as elucidate the functional and molecular role of SERPINA3 in cardiovascular (patho)physiology.Researcher(s)
- Promoter: Guns Pieter-Jan
- Co-promoter: Martinet Wim
- Fellow: Bosman Matthias
Research team(s)
Project type(s)
- Research Project
The investigation of arterial stiffness as a potential marker in cardio-oncology.
Abstract
Anthracyclines (such as doxorubicin, DOX) are among the most effective chemotherapeutics and are widely used in modern cancer treatment despite the advent of targeted therapies. However, dosedependent cardiotoxicity limits the clinical use of DOX. It is well documented that DOX may provoke cardiotoxicity leading to left ventricular dysfunction and eventually congestive heart failure. Recent studies have reported that anthracyclines also interfere with arterial stiffness, an overall measure of vascular health. However, it is unclear whether vascular toxicity occurs through the same mechanisms and pathways as the cardiac toxicity. Moreover, the clinical implications of increased arterial stiffness due to DOX, either as contributing mechanism to cardiotoxicity or as early marker of accelerated cardiovascular aging in (childhood) cancer survivors is incompletely understood. The current research proposal aims to shed light on the mechanisms and clinical relevance of DOX-induced vascular toxicity by pursuing a translational experimental research approach.Researcher(s)
- Promoter: Guns Pieter-Jan
- Fellow: Bosman Matthias
Research team(s)
Project type(s)
- Research Project