Disrupting the EMMPRIN (CD147)-Cyclophilin A Interaction Reduces Infarct Size and Preserves Systolic Function After Myocardial Ischemia and Reperfusion

作者：Seizer Peter; Ochmann Carmen; Schoenberger Tanja; Zach Sebastian; Rose Melanie; Borst Oliver; Klingel Karin; Kandolf Reinhard; MacDonald H Robson; Nowak Romana A; Engelhardt Stefan; Lang Florian; Gawaz Meinrad; May Andreas E^*

来源：Arteriosclerosis, Thrombosis, and Vascular Biology, 2011, 31(6): 1377-U316.

DOI：10.1161/ATVBAHA.111.225771

• coronary artery disease
• leukocytes
• reperfusion injury
• EMMPRIN cyclophilin A

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. (Arterioscler Thromb Vasc Biol. 2011;31:1377-1386.)

• 出版日期2011-6