Novel therapies for atherosclerotic plaque stabilization

Summary Our research focuses on understanding the molecular mechanisms that drive atherosclerotic plaque formation and plaque rupture in cardiovascular diseases. We aim to deeply characterise the fundamental molecular pathways underlying plaque formation and rupture using translational disease models and novel therapeutic agents.

Project Details

Cardiovascular diseases (CVDs), principally ischemic heart disease including myocardial infarction (heart attacks) and stroke, are the leading cause of global mortality and a major contributor to disability. The underlying cause of most CVDs is the formation of lipid-laden atherosclerotic plaques in medium and large arteries, such as those that supply the heart and brain with blood. Stable plaques grow slowly over several decades until they may cause stenosis or occlusion. Unstable or “vulnerable” plaques are prone to spontaneous erosion, fissure, or rupture, causing acute thrombosis (blood clots), occlusion, and infarction long before they cause hemodynamically significant stenosis. Majority of clinical events or CVD mortality result from unstable plaques. Thus, plaque stabilization is a promising approach to reduce morbidity and mortality.

Our research focuses on understanding the molecular mechanisms that drive atherosclerotic plaque formation and rupture in CVDs. We aim to deeply characterise the fundamental molecular pathways underlying plaque formation and rupture using novel translational disease models and cutting edge-technologies. Based on novel genomic data from polygenic risk score predictions, we identified novel targets that will be assessed to validate their causative role and therapeutic potential. We will use novel theranostic agents for diagnosis and targeted delivery of therapeutics to stabilise the vulnerable plaques. With a particular focus on translational relevance, we will assess the potential of novel therapies such as stem cell-derived exosomes and novel small-molecule inhibitors preventing plaque rupture.

In this research we will use techniques such as:

• Translational animal models
• Confocal Microscopy
• Multiphoton Microscopy
• Flow Cytometry
• Cell Culture
• Immunohistochemistry
• Molecular assays