Shear and hydrostatic stress regulate fetal heart valve remodeling through YAP-mediated mechanotransduction.

ABSTRACT: Clinically serious congenital heart valve defects arise from improper growth and remodeling of endocardial cushions into leaflets. Genetic mutations have been extensively studied but explain less than 20% of cases. Mechanical forces generated by beating hearts drive valve development, but how these forces collectively determine valve growth and remodeling remains incompletely understood. Here, we decouple the influence of those forces on valve size and shape, and study the role of YAP pathway in determining the size and shape. The low oscillatory shear stress promotes YAP nuclear translocation in valvular endothelial cells (VEC), while the high unidirectional shear stress restricts YAP in cytoplasm. The hydrostatic compressive stress activated YAP in valvular interstitial cells (VIC), wher

SUBMITTER: Wang M 

PROVIDER: S-EPMC10162797 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature