Document Type
Article
Publication Date
6-5-2012
Abstract
BACKGROUND: High shear force critically regulates platelet adhesion and thrombus formation during ischemic vascular events. To identify genetic factors that influence platelet thrombus formation under high shear stress, we performed a genome-wide association study and confirmatory experiments in human and animal platelets.
METHODS AND RESULTS: Closure times in the shear-dependent platelet function analyzer (PFA)-100 were measured on healthy, nondiabetic European Americans (n=125) and blacks (n=116). A genome-wide association (P
CONCLUSIONS: We show for the first time that (1) platelets contain supervillin; (2) platelet thrombus formation in the PFA-100 is associated with human SVIL variants and low SVIL expression; and (3) murine platelets lacking supervillin exhibit enhanced platelet thrombus formation at high shear stress. These data are consistent with an inhibitory role for supervillin in platelet adhesion and arterial thrombosis.
Recommended Citation
Edelstein, Leonard C.; Luna, Elizabeth J.; Gibson, Ian B.; Bray, Molly; Jin, Ying; Kondkar, Altaf; Nagalla, Srikanth; Hadjout-Rabi, Nacima; Smith, Tara C.; Covarrubias, Daniel; Jones, Stephen N.; Ahmad, Firdos; Stolla, Moritz; Kong, Xianguo; Fang, Zhiyou; Bergmeier, Wolfgang; Shaw, Chad; Leal, Suzanne M.; and Bray, Paul, "Human genome-wide association and mouse knockout approaches identify platelet supervillin as an inhibitor of thrombus formation under shear stress." (2012). Department of Medicine Faculty Papers. Paper 213.
https://jdc.jefferson.edu/medfp/213
PubMed ID
22550155
Comments
This article has been peer reviewed. It is the authors' final version prior to publication in Circulation
Volume 125, Issue 22, June 2012, Pages 2762-2771
The published version is available at DOI: 10.1161/CIRCULATIONAHA.112.091462 Copyright © American Heart Association