Disrupting the EMMPRIN (CD147)-cyclophilin a interaction reduces infarct size and preserves systolic function after myocardial ischemia and reperfusion

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

Research output: Contribution to journalArticle

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. 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.

Original languageEnglish (US)
Pages (from-to)1377-1386
Number of pages10
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume31
Issue number6
DOIs
StatePublished - Jun 2011

Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Seizer, P., Ochmann, C., Schönberger, T., Zach, S., Rose, M., Borst, O., Klingel, K., Kandolf, R., MacDonald, H. R., Nowak, R. A., Engelhardt, S., Lang, F., Gawaz, M., & May, A. E. (2011). Disrupting the EMMPRIN (CD147)-cyclophilin a interaction reduces infarct size and preserves systolic function after myocardial ischemia and reperfusion. Arteriosclerosis, Thrombosis, and Vascular Biology, 31(6), 1377-1386. https://doi.org/10.1161/ATVBAHA.111.225771