Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:554-559
Published online before print January 24, 2002, doi: 10.1161/hq0402.105720
Published online before print January 24, 2002, doi: 10.1161/hq0402.105720
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© 2002 American Heart Association, Inc.
Vascular Biology |
CCR2 Deficiency Decreases Intimal Hyperplasia After Arterial Injury
From The Zena and Michael A. Wiener Cardiovascular Institute (M.R., W.J.H.K., M.G., A.M., J.T.F., J.J.B., M.B.T.), Departments of Medicine (M.R., W.J.H.K., M.G., A.M., J.T.F., J.J.B., M.B.T.), Physiology and Biophysics (M.B.T.), Surgery (E.D.R.), and Pathology (J.T.F.), Mount Sinai School of Medicine, New York, NY; and Gladstone Institute of Cardiovascular Disease (I.F.C.), University of California, San Francisco.
Address correspondence to William J.H. Kim, PhD, Department of Medicine, Box 1269, Mount Sinai School of Medicine, One Gustave L. Levy Pl, New York, NY 10029-6574. E-mail william.kim{at}mssm.edu
Monocyte chemoattractant protein (MCP)-1 is upregulated in atherosclerotic plaques and in the media and intima of injured arteries. CC chemokine receptor 2 (CCR2) is the only known functional receptor for MCP-1. Mice deficient in MCP-1 or CCR2 have marked reductions in atherosclerosis. This study examines the effect of CCR2 deficiency in a murine model of femoral arterial injury. Four weeks after injury, arteries from CCR2-/- mice showed a 61.4% reduction (P<0.01) in intimal area and a 62% reduction (P<0.05) in intima/media ratio when compared with CCR2+/+ littermates. The response of CCR2+/- mice was not significantly different from that of CCR2+/+ mice. Five days after injury, the medial proliferation index, determined by bromodeoxyuridine incorporation, was decreased by 59.8% in CCR2-/- mice when compared with CCR2+/+ littermates (P<0.05). Although leukocytes rapidly adhered to the injured arterial surface, there was no significant macrophage infiltration in the arterial wall of either CCR2-/- or CCR2+/+ mice 5 and 28 days after injury. These results demonstrate that CCR2 plays an important role in mediating smooth muscle cell proliferation and intimal hyperplasia in a non-hyperlipidemic model of acute arterial injury. CCR2 may thus be an important target for inhibiting the response to acute arterial injury.
Key Words: chemokines • intimal hyperplasia • arterial injury • monocyte chemoattractant protein 1 • smooth muscle proliferation
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