Étude du rôle de la lipoprotéine(a) dans le rétrécissement aortique calcifié

 

Benoit Arsenault

Institut universitaire de cardiologie et de pneumologie de Québec [IUCPQ]

 

Domaine : neurosciences, santé mentale et toxicomanies

Programme Chercheurs-boursiers - Junior 2

Concours 2018-2019

Calcific aortic valve stenosis (CAVS) is the most common form of heart valve diseases affecting almost 3% of the population older than 65 and the prevalence of this disease is expected to double within the next 20 years. Our team has reported that a genetic variant at the LPA locus is strongly associated with circulating Lipoprotein(a) [Lp(a)] levels and CAVS risk. We also reported that patients with high Lp(a) levels have a much faster CAVS progression compared to patients with low Lp(a) levels. We also recently found that Lp(a)-derived autotaxin promotes inflammation and mineralization of the aortic valve.

This research program aims at using state-of-the-art imaging with 18F-NaF PET/CT and transcriptomic and proteomic techniques to determine the importance of Lp(a) screening for the identification of patients at high risk for future CAVS and to identify the precise mechanisms through which Lp(a) causes CAVS.

We propose to investigate the association between Lp(a) levels and aortic valve microcalcification and/or macrocalcification in four types of populations who could be at high CAVS risk such as patients with elevated Lp(a) levels with or without CAVS, first-degree relatives of patients with CAVS and elevated Lp(a) levels and patients with familial hypercholesterolemia. We will also use a "multi-omics" approach (genomics, transcriptomics, proteomics and lipidomics) to identify the pathophysiological mechanisms through which Lp(a) causes CAVS.

Ultimately, my objective is to determine whether measuring Lp(a) levels could be clinically useful in patients with CAVS, but also to show that targeting Lp(a) with therapeutic agents could prevent CAVS development in high-risk patients.