Scientific topics
Keywords
Célia Bourguignon Role of microvascular disease in the pathophysiology of heart failure
Course and current status
PhD Cellular biology and pathophysiology
Scientific summary
Heart failure (HF) is one of the main causes of death and morbidity in western country. Therapeutic progresses have been made to improve the prognosis of the main form of heart failure i.e. heart failure with reduced ejection fraction. However, the prevalence of heart failure with preserved ejection fraction (HFpEF) is constantly increasing as the population age and will soon turn into the most common heart failure phenotype. And, to date, there are no approved therapies available to reduce mortality or hospitalization for these patients. There is, then, an urgent need to understand HFpEF pathophysiology in order to develop new drugs.
Cardiac microvascular dysfunction is suspected to promote HFpEF. The present thesis proposal wishes to clarify HFpEF pathophysiology (1) by identifying new molecular mechanisms controlling vascular integrity in the heart and (2) by evaluating the specific consequences of endothelial cell dysfunction on heart structure and function. To verify this hypothesis, the PhD student will perform both in vitro (cell culture) and in vivo (mouse model)assays in which loss of function (blocking antibodies, siRNA, dominant negative, conditional KO mice) and gain of function (transfections, gene therapy, small molecule agonist) strategies will be used.
