Grant: CIHR Fellowship

Valvular heart diseases are an important and growing public health problem in developed societies. Aortic valvular stenosis (AVS) is the most common valvular disease which is present in more than 3% of patients older than 65 years. We believe that identifying the risk factors as well as the biological mechanisms involved in the pathophysiology of AVS is of critical importance to identify individuals at high risk for AVS, but also to identify the biological mediators that could be targeted to stop the progression of this disease. Although the genetic and molecular mechanisms that influence the progression of this disease have yet to be identified. We have recently tested the hypothesis that high-density lipoprotein (HDL) cholesterol (often referred to as the good cholesterol) may be involved in the progression of AVS. By treating a group of rabbits predisposed to AVS with a pharmacological compound that raises HDL cholesterol levels while improving its quality, we have recently shown that the clinical indices associated with the progression of AVS were significantly improved compared to rabbits treated with a placebo. This finding has prompted us to launch a series of investigations in humans aiming at studying the relationship between the genes as well as the circulating biomarkers involved in HDL metabolism and the progression of aortic stenosis in humans. At the Montreal Heart Institute, we have a direct access to several hundreds of patients that meet the clinical criteria for AVS and we aim at taking advantage of our expertise in patient care as well as in cardiovascular genomics to unravel the link between HDL and AVS. For that purpose, we will establish the relationship between variants in genes related to HDL metabolism and the risk of AVS and we will perform several assays to test the hypothesis that the HDL of patients with AVS have an impaired ability to reduce the calcification process in human vascular interstitial cells.