title: MCP-1 deficiency is associated with reduced intimal hyperplasia after arterial injury.
abstract: 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.
authors.affiliation: The Zena and Michael A Wiener Cardiovascular Institute, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: William J H
authors.initials: WJ
authors.lastname: Kim
authors.forename: Igor
authors.initials: I
authors.lastname: Chereshnev
authors.forename: Mihaela
authors.initials: M
authors.lastname: Gazdoiu
authors.forename: John T
authors.initials: JT
authors.lastname: Fallon
authors.forename: Barrett J
authors.initials: BJ
authors.lastname: Rollins
authors.forename: Mark B
authors.initials: MB
authors.lastname: Taubman
mesh_terms: 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*
chemical_list: C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D018925:Chemokines; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D004247:DNA; D001973:Bromodeoxyuridine