| Disrupting the EMMPRIN (CD147)-cyclophilin A interaction reduces infarct size and preserves systolic function after myocardial ischemia and reperfusion. | |
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MedLine Citation:
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PMID: 21441138 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: Inflammation and proteolysis crucially contribute to myocardial ischemia and reperfusion injury. The extracellular matrix metalloproteinase inducer EMMPRIN (CD147) and its ligand cyclophilin A (CyPA) may be involved in both processes. The aim of the study was to characterize the role of the CD147 and CyPA interplay in myocardial ischemia/reperfusion (I/R) injury. METHODS AND RESULTS: Immunohistochemistry showed enhanced expression of CD147 and CyPA in myocardial sections from human autopsies of patients who had died from acute myocardial infarction and from mice at 24 hours after I/R. At 24 hours and 7 days after I/R, the infarct size was reduced in CD147(+/-) mice vs CD147(+/+) mice (C57Bl/6), in mice (C57Bl/6) treated with monoclonal antibody anti-CD147 vs control monoclonal antibody, and in CyPA(-/-) mice vs CyPA(+/+) mice (129S6/SvEv), all of which are associated with reduced monocyte and neutrophil recruitment at 24 hours and with a preserved systolic function at 7 days. The combination of CyPA(-/-) mice with anti-CD147 treatment did not yield further protection compared with either inhibition strategy alone. In vitro, treatment with CyPA induced monocyte chemotaxis in a CD147- and phosphatidylinositol 3-kinase-dependent manner and induced monocyte rolling and adhesion to endothelium (human umbilical vein endothelial cells) under flow in a CD147-dependent manner. CONCLUSION: CD147 and its ligand CyPA are inflammatory mediators after myocardial ischemia and reperfusion and represent potential targets to prevent myocardial I/R injury. |
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Authors:
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Peter Seizer; Carmen Ochmann; Tanja Schönberger; Sebastian Zach; Melanie Rose; Oliver Borst; Karin Klingel; Reinhard Kandolf; H Robson MacDonald; Romana A Nowak; Stefan Engelhardt; Florian Lang; Meinrad Gawaz; Andreas E May |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-03-24 |
Journal Detail:
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Title: Arteriosclerosis, thrombosis, and vascular biology Volume: 31 ISSN: 1524-4636 ISO Abbreviation: Arterioscler. Thromb. Vasc. Biol. Publication Date: 2011 Jun |
Date Detail:
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Created Date: 2011-05-19 Completed Date: 2011-07-26 Revised Date: 2012-09-20 |
Medline Journal Info:
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Nlm Unique ID: 9505803 Medline TA: Arterioscler Thromb Vasc Biol Country: United States |
Other Details:
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Languages: eng Pagination: 1377-86 Citation Subset: IM |
Affiliation:
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Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Eberhard Karls-Universität Tübingen, Germany. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antigens, CD147 / analysis, physiology* Cell Adhesion Cell Movement Cyclophilin A / analysis, physiology* Humans Macrophages / physiology Mice Mice, Inbred C57BL Myocardial Infarction / metabolism* Myocardial Ischemia / physiopathology* Myocardial Reperfusion Injury / etiology*, prevention & control Neutrophils / physiology Systole* |
| Grant Support | |
ID/Acronym/Agency:
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HD40093/HD/NICHD NIH HHS; U54 HD040093-05/HD/NICHD NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/BSG protein, human; 0/Bsg protein, mouse; 136894-56-9/Antigens, CD147; EC 5.2.1.-/Cyclophilin A |
| Comments/Corrections | |
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