CCR2 deficiency decreases intimal hyperplasia after arterial injury.
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.
Roque
Merce
M
Zena and Michael A. Wiener Cardiovascular Institute, Department of Medicine, Mount Sinai School of Medicine, New York, NY, USA.
Kim
William J H
WJ
Gazdoin
Michaela
M
Malik
Alia
A
Reis
Ernane D
ED
Fallon
John T
JT
Badimon
Juan J
JJ
Charo
Israel F
IF
Taubman
Mark B
MB
D000818:Animals; D002455:Cell Division; D018932:Chemokine CCL2 / Q000172:deficiency / Q000378:metabolism*; D005260:Female; D005263:Femoral Artery / Q000473:pathology; D006965:Hyperplasia / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000172:deficiency* / Q000378:metabolism; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology*
C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D054390:Receptors, CCR2; D019707:Receptors, Chemokine