Age-associated methionine sulfoxide reductase A protects against valvular interstitial cell senescence and valvular calcification.

Abstract

Calcific aortic valve disease (CAVD) is a cardiovascular disease prevalent in the aging population, resulting in high morbidity and mortality rates. However, the molecular mechanisms underlying CAVD remain unclear. We initially conducted an RNA sequencing analysis of aortic valve leaflets from rats of different ages to identify key genes involved in valvular aging and calcification. Bioinformatics analysis demonstrated that methionine sulfoxide reductase A (MSRA) was crucial to valvular calcification and senescence. To further investigate whether and how MSRA influences CAVD pathogenesis, we utilized two in vitro models: a human valvular interstitial cell (VIC) calcification model induced by osteogenic medium, and a VIC senescence model induced by hydrogen peroxide. Western blotting, immunofluorescence, flow cytometry, and alkaline phosphatase staining were conducted to evaluate the changes in calcific nodule formation and senescent markers. In vivo, ApoE