Absence of CC chemokine receptor-2 reduces atherosclerosis in apolipoprotein E-deficient mice

The accumulation of circulating monocytes in the arterial wall is an early event in atherosclerotic plaque formation. Monocyte chemoattractant protein -1 (MCP-1) has been implicated as the primary source of monocyte chemoattra ctant functioning in these early stages of atherogenesis. To determine whet her the receptor for MCP-I, CC chemokine receptor CCR2, plays a role in ath erogenesis, CCR2-deficient animals were crossed with mice lacking apo E, a well characterized model of atherosclerosis. While lipid levels were unchan ged, the double knockout mice exhibited a 3-fold reduction in mean aortic l esion area compared to apo E-deficient control mice. Furthermore, the lesio ns in the double mutants were less advanced, consisting primarily of foam c ell deposits and fatty streaks located on or directly adjacent to the aorti c valve attachment sites. These studies directly demonstrate that the MCP-1 receptor, CCR2, plays an important role in atherogenesis. (C) 1999 Elsevie r Science Ireland Ltd. All rights reserved.