Yin and Yang of MCP-1

Abstract

See related article, pages 881–889 Monocyte chemoattractant protein-1 (MCP-1, also known as CCL2) is a chemokine of the C-C type which recruits circulating monocytes to sites of inflammation. Over the past several years, MCP-1 has become established as a major factor in the development of atherosclerosis through its promotion of monocyte/macrophage accumulation in atherosclerotic plaques, leading in turn to chronic inflammation, smooth muscle cell proliferation, and plaque instability.1 Although not present in normal blood vessels, MCP-1 protein and mRNA are strongly expressed in areas of atherosclerosis.2,3 Knock out of the MCP-1 gene or the receptor for MCP-1, C-C chemokine receptor (CCR)-2, are associated with a decrease in the extent of atherosclerosis in murine models.4,5 MCP-1 is produced by endothelial cells, vascular smooth muscle cells, and macrophages in atherosclerotic plaques. Oxidized LDL in the arterial wall may upregulate the MCP-1 gene in vascular cells and stimulate the local adhesion of monocytes to endothelial cells.6 LDL-C has been shown to upregulate CCR-2 expression on monocytes, and monocyte CCR2 expression is dramatically increased in hypercholesterolemic patients compared with normal controls.7 There has been increasing interest in the role of MCP-1 in other inflammatory conditions, including post-ischemic inflammation. A study published in this issue of Circulation Research by Dewald et al demonstrates that MCP-1 plays an important role in the healing of necrotic areas of myocardium following coronary artery occlusion and reperfusion.8 Mice with disruption of the MCP-1 gene exhibited striking delays in the recruitment of macrophages into the healing infarct and in the replacement of injured myocytes by granulation tissue without any effect on neutrophil mobilization. MCP-1 null mice had decreased and delayed infiltration of macrophages, …