title: Disrupting the EMMPRIN (CD147)-cyclophilin A interaction reduces infarct size and preserves systolic function after myocardial ischemia and reperfusion.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  CD147 and its ligand CyPA are inflammatory mediators after myocardial ischemia and reperfusion and represent potential targets to prevent myocardial I/R injury.
authors: Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Eberhard Karls-Universität Tübingen, Germany.
authors: Peter
authors: P
authors: Seizer
authors: Carmen
authors: C
authors: Ochmann
authors: Tanja
authors: T
authors: Schönberger
authors: Sebastian
authors: S
authors: Zach
authors: Melanie
authors: M
authors: Rose
authors: Oliver
authors: O
authors: Borst
authors: Karin
authors: K
authors: Klingel
authors: Reinhard
authors: R
authors: Kandolf
authors: H Robson
authors: HR
authors: MacDonald
authors: Romana A
authors: RA
authors: Nowak
authors: Stefan
authors: S
authors: Engelhardt
authors: Florian
authors: F
authors: Lang
authors: Meinrad
authors: M
authors: Gawaz
authors: Andreas E
authors: AE
authors: May
mesh_terms: D000818:Animals; D051926:Basigin / Q000032:analysis / Q000502:physiology*; D002448:Cell Adhesion; D002465:Cell Movement; D021984:Cyclophilin A / Q000032:analysis / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000209:etiology* / Q000517:prevention & control; D009504:Neutrophils / Q000502:physiology; D013599:Systole
chemical_list: C497886:BSG protein, human; C497887:Bsg protein, mouse; D051926:Basigin; D021984:Cyclophilin A