The Pathogenic Roles of Local Vitamin D Metabolism Defect in Valve Inflammation and Calcification.

ABSTRACT: Calcific aortic valve disease (CAVD) is a highly prevalent disease that leads to heart failure. However, the pathogenesis of CAVD remains poorly understood, and the disease currently lacks medicinal treatment. In this study, utilizing a high-phosphate-diet-induced valvular calcification model in conjunction with single-cell profiling and genetic tracing, two subpopulations of Prrx1⁺Acta2^- valve interstitial cells (VICs) are identified that underwent osteogenic differentiation. Mechanistically, elevated phosphate suppresses the expression of vitamin D metabolism genes primarily in VICs and response genes in immune cells, leading to local activation of CD8⁺ T cells, macrophages, and Prox1⁺ endothelial cells in the valve. It is further shown that in

SUBMITTER: Yang R 

PROVIDER: S-EPMC12752593 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature