MCP-1 deficiency is associated with reduced intimal hyperplasia after arterial injury

• Published in: Biochemical and biophysical research communications Vol. 310; no. 3; pp. 936 - 942
• Main Authors: Kim, William J.H, Chereshnev, Igor, Gazdoiu, Mihaela, Fallon, John T, Rollins, Barrett J, Taubman, Mark B
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 24.10.2003
• Subjects: Animals; Arterial injury; Arteries - injuries; Bromodeoxyuridine - pharmacology; Cell Division; Cell Movement; Chemokine CCL2 - deficiency; Chemokine CCL2 - genetics; Chemokine CCL2 - physiology; Chemokines; Chemokines - metabolism; DNA - biosynthesis; DNA - metabolism; Femoral Artery - pathology; Hyperplasia; Immunohistochemistry; Intimal hyperplasia; Macrophages - metabolism; Mice; Mice, Transgenic; Monocyte chemoattractant protein 1; Muscle, Smooth - pathology; Receptors, CCR2; Receptors, Chemokine - metabolism; Smooth muscle proliferation; Tunica Intima - pathology; Smooth muscle proliferation; Arterial injury; Intimal hyperplasia; Chemokines; Monocyte chemoattractant protein 1
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2003.09.088

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 ≈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 ≈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.