The dimeric platelet collagen receptor GPVI-Fc reduces platelet adhesion to activated endothelium and preserves myocardial function after transient ischemia in mice
| Autor: | Melanie Ziegler, Bernhard Nieswandt, Götz Münch, Ildiko Konrad, Carmen Ochmann, Klaus T. Preissner, Tobias Jürgens, Margitta Elvers, Steffen Massberg, Peter Seizer, Tanja Schönberger, Meinrad Gawaz, Oliver Borst, Harald F. Langer, Martin Ungerer |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Physiology CHO Cells Platelet Membrane Glycoproteins Platelet membrane glycoprotein Collagen receptor Proinflammatory cytokine Mice Cricetulus Platelet Adhesiveness Platelet degranulation Cricetinae Platelet adhesiveness Human Umbilical Vein Endothelial Cells Animals Humans Platelet Platelet activation Chemistry Heart Cell Biology Immunoglobulin Fc Fragments Cell biology Mice Inbred C57BL Ischemic Attack Transient Immunology Cattle Endothelium Vascular Protein Multimerization GPVI |
| Zdroj: | American Journal of Physiology-Cell Physiology. 303:C757-C766 |
| ISSN: | 1522-1563 0363-6143 |
| DOI: | 10.1152/ajpcell.00060.2012 |
| Popis: | Platelets play a critical role in the pathophysiology of reperfusion, sepsis, and cardiovascular diseases. In a multiple step process, they adhere to activated endothelium and release proinflammatory cytokines thereby promoting the inflammatory process. Glycoprotein VI (GPVI) is the major collagen receptor on the platelet surface and triggers platelet activation and primary hemostasis. Activation of GPVI leads to stable platelet adhesion and degranulation of platelet granules. However, GPVI is critically involved in platelet adhesion to activated endothelium without exposure of subendothelial matrix. Earlier studies show that the soluble GPVI-Fc binds to collagen and protects mice from atherosclerosis and decreases neointima proliferation after arterial injury. Here, we show for the first time that recombinant GPVI-Fc binds to activated endothelium mainly via vitronectin and prevents platelet/endothelial interaction. Administration of GPVI-Fc reduced infarct size and preserved cardiac function in a mouse model of myocardial infarction. This process was associated with reduced GPVI-induced platelet degranulation and release of proinflammatory cytokines in vitro and in vivo. Taken together, administration of GPVI-Fc offers a novel strategy to control platelet-mediated inflammation and to preserve myocardial function following myocardial infarction. |
| Databáze: | OpenAIRE |
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