MCP-1 deficiency is associated with reduced intimal hyperplasia after arterial injury.
Monocyte chemoattractant protein (MCP)-1 is abundant in smooth muscle cells (SMC) and macrophages of atherosclerotic plaques and in the injured arterial wall. MCP-1 and its receptor, CCR2, are important mediators of macrophage accumulation and atherosclerotic plaque progression. We have recently reported that CCR2(-/-) mice have a approximately 60% decrease in intimal hyperplasia and medial DNA synthesis in response to femoral arterial injury. We have now examined the response to femoral arterial injury in MCP-1(-/-) mice. MCP-1 deficiency was associated with a approximately 30% reduction in intimal hyperplasia at 4 weeks and was not associated with diminished medial DNA synthesis. Despite inducing tissue factor in SMC culture, MCP-1 deficiency was not associated with a decrease in neointimal tissue factor after injury. These data suggest that MCP-1 and CCR2 deficiencies have distinct effects on arterial injury. The effects of MCP-1 on intimal hyperplasia may be mediated largely through SMC migration.
Kim
William J H
WJ
The Zena and Michael A Wiener Cardiovascular Institute, Mount Sinai School of Medicine, New York, NY, USA.
Chereshnev
Igor
I
Gazdoiu
Mihaela
M
Fallon
John T
JT
Rollins
Barrett J
BJ
Taubman
Mark B
MB
D000818:Animals; D001158:Arteries / Q000293:injuries*; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002455:Cell Division; D002465:Cell Movement; D018932:Chemokine CCL2 / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D018925:Chemokines / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis / Q000378:metabolism; D005263:Femoral Artery / Q000473:pathology; D006965:Hyperplasia; D007150:Immunohistochemistry; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009130:Muscle, Smooth / Q000473:pathology; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000378:metabolism; D017539:Tunica Intima / Q000473:pathology*
C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D018925:Chemokines; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D004247:DNA; D001973:Bromodeoxyuridine