Reduced Proteolytic Cleavage of von Willebrand Factor Leads to Aortic Valve Stenosis and Load-Dependent Ventricular Remodeling.

ABSTRACT: We hypothesized that excess endothelial-associated von Willebrand factor (vWF) and secondary platelet adhesion contribute to aortic valve stenosis (AS). We studied hyperlipidemic mice lacking ADAMTS13 (LDLR ^-/- AD13 ^-/- ), which cleaves endothelial-associated vWF multimers. On echocardiography and molecular imaging, LDLR ^-/- AD13 ^-/- compared with control strains had increased aortic endothelial vWF and platelet adhesion and developed hemodynamically significant AS, arterial stiffening, high valvulo-aortic impedance, and secondary load-dependent reduction in LV systolic function. Histology revealed leaflet thickening and calcification with valve interstitial cell myofibroblastic and osteogen

SUBMITTER: Ozawa K 

PROVIDER: S-EPMC9357566 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature