Inhibition of MCP-1/CCR2 Signaling Does Not Inhibit Intimal Proliferation in a Mouse Aortic Transplant ModelAlexis J.D.a · Pyo R.T.b, c · Chereshnev I.b, c · Katz J.f · Rollins B.J.d · Charo I.F.e · Taubman M.B.a
aAab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, N.Y., bZena and Michael A. Wiener Cardiovascular Institute and cDepartment of Medicine, Mount Sinai School of Medicine, New York, N.Y., dDepartment of Adult Oncology, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass., and eGladstone Institute of Cardiovascular Disease, University of California, San Francisco, San Francisco, Calif., USA; fSackler School of Medicine, Tel Aviv, Israel
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Article / Publication Details
Background: Transplant arteriopathy is the leading cause of long term morbidity and mortality following heart transplantation. Animal models have demonstrated that monocyte chemoattractant protein (MCP)-1 is induced early after transplant in cardiac and aortic allografts. We have previously reported that deficiency of MCP-1 or its receptor, CC chemokine receptor 2 (CCR2), is associated with a reduction in intimal proliferation in a mouse femoral artery injury model. Using knockout mice, we have now examined the role of MCP-1 and CCR2 in the development of the intimal proliferation of transplant arteriopathy. Methods: C57Bl/6 CCR2 and MCP-1 wild-type and knockout mice were used in the studies and aortic transplants were performed between Balb/c mice and C57Bl/6 mice. Aortas from recipient animals were harvested 8 weeks after transplant. Results: Unlike arterial injury, in an aortic transplant model inhibition of MCP-1/CCR2 signaling did not result in reduced intimal proliferation. Conclusions: Despite a pathology that appears similar, the inflammatory mediators that regulate transplant arteriopathy differ from those regulating intimal proliferation secondary to wire injury. Our results suggest that targeting MCP-1/CCR2 signaling is not sufficient to block transplant arteriopathy across a complete MHC-mismatch barrier.
© 2008 S. Karger AG, Basel
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