ABSENCE OF MONOCYTE CHEMOATTRACTANT PROTEIN-1 REDUCES ATHEROSCLEROSISIN LOW-DENSITY-LIPOPROTEIN RECEPTOR-DEFICIENT MICE

Recruitment of blood monocytes into the arterial subendothelium is one of the earliest steps in atherogenesis. Monocyte chemoattractant prot ein-1 (MCP-1), a CC chemokine, is one likely signal involved in this p rocess. To test MCP-l's role in atherogenesis, low density lipoprotein (LDL) receptor-deficient mice were made genetically deficient for MCP -1 and fed a high cholesterol diet. Despite having the same amount of total and fractionated serum cholesterol as LDL receptor-deficient mic e with wild-type MCP-1 alleles, LDL receptor/MCP-1-deficient mice had 83% less lipid deposition throughout their aortas. Consistent with MCP -l's monocyte chemoattractant properties, compound-deficient mice also had fewer macrophages in their aortic walls. Thus, MCP-1 plays a uniq ue and crucial role in the initiation of atherosclerosis and may provi de a new therapeutic target in this disorder.