Distributed flow increases UBE2C (Ubiquitin E2 Ligase C) via loss of miR-483-3p, inducing aortic valve calcification by the pVHL (von Hippel-Lindau Protein) and HIF-1α (Hypoxia-Inducible Factor-1α) pathway in endothelial cells

Autores/as

Fernandez Esmerats, J.; Villa-Roel, N.; Kumar, S.; Gu, L.; Salim, M. T.; Ohh, M.; Taylo, W. R.; Nerem, R. M.; Yoganathan, A. P.; Jo, H.

Abstract

Calcific aortic valve (AV) disease, characterized by AV sclerosis and calcification, is a major cause of death in the aging population; however, there are no effective medical therapies other than valve replacement. AV calcification preferentially occurs on the fibrosa side, exposed to disturbed flow (d-flow), whereas the ventricularis side exposed to predominantly stable flow remains protected by unclear mechanisms. Here, we tested the role of novel flow-sensitive UBE2C (ubiquitin E2 ligase C) and microRNA-483-3p (miR-483) in flow-dependent AV endothelial function and AV calcification.