Document Detail


Disrupting the EMMPRIN (CD147)-cyclophilin A interaction reduces infarct size and preserves systolic function after myocardial ischemia and reperfusion.
MedLine Citation:
PMID:  21441138     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-03-24
Journal Detail:
Title:  Arteriosclerosis, thrombosis, and vascular biology     Volume:  31     ISSN:  1524-4636     ISO Abbreviation:  Arterioscler. Thromb. Vasc. Biol.     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-05-19     Completed Date:  2011-07-26     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  9505803     Medline TA:  Arterioscler Thromb Vasc Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1377-86     Citation Subset:  IM    
Affiliation:
Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Eberhard Karls-Universität Tübingen, Germany.
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MeSH Terms
Descriptor/Qualifier:
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:
HD40093/HD/NICHD NIH HHS; U54 HD040093-05/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
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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