Mitochondrially Mediated Integrin alpha(IIb)beta(3) Protein Inactivation Limits Thrombus Growth

• Type of Material: Article
• Authors: Fang Liu, Emory University; Graciela Gamez, Emory University; David R Myers, Emory University; Wayne Clemmons, Emory University; Wilbur Lam, Emory University; Shawn M. Jobe, Emory University
• Language: English
• Date: 2013-10-18
• Publisher: American Society for Biochemistry and Molecular Biology
• Publication Version: Final Published Version
• Copyright Statement: © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.
• Final Published Version (URL): http://dx.doi.org/10.1074/jbc.M113.472688
• Title of Journal or Parent Work: Journal of Biological Chemistry
• ISSN: 0021-9258
• Volume: 288
• Issue: 42
• Start Page: 30672
• End Page: 30681
• Grant/Funding Information: This work was supported, in whole or in part, by National Institutes of Health grant HL095858.; This work was also supported by American Heart Association Fellow-to-Faculty Transition Award 2006-2011.
• Keywords: PHOSPHATIDYLSERINE EXPOSURE; NA+/H+ EXCHANGER; Biochemistry & Molecular Biology; CYTOPLASMIC DOMAIN; BLEEDING DISORDER; PERMEABILITY TRANSITION PORE; Mitochondria; CALPAIN CLEAVAGE; COATED-PLATELET FORMATION; PROCOAGULANT ACTIVITY; Calpain; Science & Technology; Integrin; Platelets; ADHERENT PLATELETS; Thrombosis; VON-WILLEBRAND-FACTOR; Life Sciences & Biomedicine
• Research Categories: Health Sciences, Medicine and Surgery; Engineering, Biomedical

Abstract

Background: Changes in integrin αIIbβ3 binding affinity occur in strongly stimulated platelets. Results: Platelet mitochondrial permeability transition pore formation enhances calpain activity, which leads to integrin β3-associated proteolytic cleavage and integrin inactivation. Conclusion: Mitochondrially mediated integrin αIIbβ3 inactivation limits platelet aggregation and thrombus growth. Significance: Modulation of this pathway may offer a novel alternative for the prevention of thrombosis.