Grant: Early Career Investigator Awards - Lipoprotein Metabolism

Calcific aortic valve stenosis (CAVS) is the most common form of heart valve diseases, affecting almost 3% of the population older than 65. CAVS is caused by the calcification of cells in the aortic valve. No pharmacological agents have been proven effective in the treatment of CAVS. Our team has identified a particle carried in the blood called lipoprotein(a) (Lp[a]) as one of the strongest risk factor for CAVS. The objective of this research project aims at utilizing novel and innovative approaches to show that Lp(a) is not only a marker of CAVS risk but a causal risk factor that plays a crucial role in the pathophysiology of CAVS. More specifically, the first objective of this project is to determine whether patients with CAVS and high Lp(a) levels have family relatives that have high Lp(a) levels who could be at risk for CAVS. Our second objective is to investigate the role of the proteome of Lp(a) (other proteins that are carried by Lp[a]) in key steps of valvular calcification. Our team has been working in collaboration with Ionis pharmaceuticals, a pharmaceutical company that is currently developing a compound that has recently been shown to lower Lp[a] levels by 80%) to identify patients with high Lp(a) levels and CAVS. The objective of our project called ATLAS (Assessment and Treatment of Lipoprotein[a] in Aortic Stenosis) project that has recently been launched at our institution is to determine the feasibility of a Lp(a)-lowering trial with this compound in patients with CAVS. Our objective is to take advantage of this partnership with the industry and the Lipoprotein(a) Foundation to further expand this unique cohort to families of affected individuals and to gain new valuable knowledge into the biological mechanisms that link high Lp(a) with CAVS.