Human Genome-Wide Association and Mouse Knockout Approaches Identify Platelet Supervillin as an Inhibitor of Thrombus Formation Under Shear Stress

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 anima...

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Bibliographic Details
Published in:Circulation (New York, N.Y.) N.Y.), 2012-06, Vol.125 (22), p.2762-2771
Main Authors: EDELSTEIN, Leonard C, LUNA, Elizabeth J, JONES, Stephen N, AHMAD, Firdos, STOLLA, Moritz, XIANGUO KONG, ZHIYOU FANG, BERGMEIER, Wolfgang, SHAW, Chad, LEAL, Suzanne M, BRAY, Paul F, GIBSON, Ian B, BRAY, Molly, YING JIN, KONDKAR, Altaf, NAGALLA, Srikanth, HADJOUT-RABI, Nacima, SMITH, Tara C, COVARRUBIAS, Daniel
Format: Article
Language:English
Subjects:
Adult
African Americans - genetics
Animals
Biological and medical sciences
Blood and lymphatic vessels
Blood Platelets - cytology
Blood Platelets - physiology
Blood vessels and receptors
Cardiology. Vascular system
Cell Size
Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous
European Continental Ancestry Group - genetics
Female
Fundamental and applied biological sciences. Psychology
Genome-Wide Association Study
Genotype
Humans
Male
Medical sciences
Membrane Proteins - genetics
Membrane Proteins - physiology
Mice
Mice, Inbred C57BL
Mice, Knockout
Microfilament Proteins - genetics
Microfilament Proteins - physiology
Middle Aged
Models, Animal
Platelet Adhesiveness - physiology
Polymorphism, Single Nucleotide - genetics
Stress, Mechanical
Thrombosis - physiopathology
Vertebrates: cardiovascular system
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Summary: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. 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
ISSN:0009-7322
1524-4539
DOI:10.1161/CIRCULATIONAHA.112.091462