Localisation of mRNA for JE/MCP-1 and its receptor CCR2 in atheroscleroticlesions of the ApoE knockout mouse

MCP-1 has potent chemotactic activity for monocytes and is strongly implica ted in the pathogenesis of atherosclerosis. In the present study, we have u sed in situ hybridisation to examine the gene expression of JE, the murine homologue of MCP-1, and its receptor, CCR2, during the development of ather osclerotic lesions in the ApoE knockout mouse, interestingly, the earliest expression of JE detected during lesion development was found to be localis ed in mesenchymal cells in the adventitia and not in the intima. Macrophage s were subsequently found to accumulate in these affected regions of the ad ventitia and these cells were found to express high levels of JE. At this s tage, early macrophage-rich lesions with high expression of JE were also se en in the intima, but expression of mRNA for the receptor for JE (CCR2) was only found on adventitial macrophages and not in the intima. This sequence of events suggests that adventitial inflammation may be an important early event in lesion development and responsible for the subsequent accumulatio n of macrophages in the intima possibly by recruitment from the adventitia as well as via the vessel lumen. Copyright (C) 2000 S. Karger AG, Basel.