Multi-omic analyses identified proteins involved in activation cascades and genes related to cardiac aging and inflammation as biological pathways linking Lp(a) to calcific aortic valve stenosis.
Observational (n=161)
What are the proteomic and transcriptomic pathways linking Lipoprotein(a) levels to calcific aortic valve stenosis?
Multi-omic analyses identified biological pathways, including inflammation and chondrocyte development, through which Lipoprotein(a) may promote calcific aortic valve stenosis.
Lipoprotein(a) (Lp(a)) is one of the most important risk factors for the development of calcific aortic valve stenosis (CAVS). However, the mechanisms through which Lp(a) causes CAVS are currently unknown. Our objectives were to characterize the Lp(a) proteome and to identify proteins that may be differentially associated with Lp(a) in patients with versus without CAVS. Our second objective was to identify genes that may be differentially regulated by exposure to high versus low Lp(a) levels in explanted aortic valves from patients with CAVS. We isolated Lp(a) from the blood of 21 patients with CAVS and 22 volunteers and performed untargeted label-free analysis of the Lp(a) proteome. We also investigated the transcriptomic signature of calcified aortic valves from patients who underwent aortic valve replacement with high versus low Lp(a) levels (n = 118). Proteins involved in the protein activation cascade, platelet degranulation, leukocyte migration, and response to wounding may be associated with Lp(a) depending on CAVS status. The transcriptomic analysis identified genes involved in cardiac aging, chondrocyte development, and inflammation as potentially influenced by Lp(a). Our multi-omic analyses identified biological pathways through which Lp(a) may cause CAVS, as well as key molecular events that could be triggered by Lp(a) in CAVS development.
Bourgeois et al. (Fri,) conducted a observational in Calcific aortic valve stenosis (CAVS) (n=161). High Lp(a) levels / CAVS status vs. Low Lp(a) levels / without CAVS was evaluated on Lp(a) proteome characterization and transcriptomic signature of calcified aortic valves. Multi-omic analyses identified proteins involved in activation cascades and genes related to cardiac aging and inflammation as biological pathways linking Lp(a) to calcific aortic valve stenosis.