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

Koya Ozawa, Matthew A. Muller, Oleg Varlamov, Matthew W. Hagen, William Packwood, Terry K. Morgan, Aris Xie, Claudia S. López, Dominic Chung, Junmei Chen, José A. López, Jonathan R. Lindner

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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 osteogenic transformation, and evidence for TGFβ1 pathway activation. We conclude that valve leaflet endothelial vWF-platelet interactions promote AS through juxtacrine platelet signaling.

Original languageEnglish (US)
Pages (from-to)642-655
Number of pages14
JournalJACC: Basic to Translational Science
Volume7
Issue number7
DOIs
StatePublished - Jul 2022

Keywords

  • aortic valve stenosis
  • echocardiography
  • von Willebrand factor

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Fingerprint

Dive into the research topics of 'Reduced Proteolytic Cleavage of von Willebrand Factor Leads to Aortic Valve Stenosis and Load-Dependent Ventricular Remodeling'. Together they form a unique fingerprint.

Cite this