Localisation of mRNA for JE/MCP-1 and Its Receptor CCR2 in Atherosclerotic Lesions of the ApoE Knockout Mouse

Abstract

MCP-1 has potent chemotactic activity for monocytes and is strongly implicated in the pathogenesis of atherosclerosis. In the present study, we have used in situ hybridisation to examine the gene expression of JE, the murine homologue of MCP-1, and its receptor, CCR2, during the development of atherosclerotic lesions in the ApoE knockout mouse. Interestingly, the earliest expression of JE detected during lesion development was found to be localised in mesenchymal cells in the adventitia and not in the intima. Macrophages were subsequently found to accumulate in these affected regions of the adventitia and these cells were found to express high levels of JE. At this stage, early macrophage-rich lesions with high expression of JE were also seen 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 accumulation of macrophages in the intima possibly by recruitment from the adventitia as well as via the vessel lumen.

Adeno-associated virus vector-mediated interleukin-10 gene transfer inhibits atherosclerosis in apolipoprotein E-deficient mice

“…24,25 In our study, we demonstrated that serum MCP-1 concentrations are significantly lower in IL-10-transduced mice than in control mice. In addition, we observed enhanced MCP-1 expression in the vascular wall of ApoE-deficient mice, as reported previously, 26 which was significantly inhibited by IL-10 gene transfer. Moreover, the extent of atherosclerotic lesion formation was significantly decreased in AAV5-mIL10-transduced mice, and positively correlated with serum MCP-1 concentration.…”

Laser capture microdissection analysis of gene expression in macrophages from atherosclerotic lesions of apolipoprotein E-deficient mice

“…3). These three genes were chosen for study because their products are implicated in atherogenesis, as reflected by being upregulated in human coronary plaque (27)(28)(29) and in lesions of animal models of atherosclerosis (18,30,31). More direct support for causative roles has come from recent mouse studies.…”

Monocyte Chemoattractant Protein-1 and 5-Lipoxygenase Products Recruit Leukocytes in Response to Platelet-Activating Factor-Like Lipids in Oxidized Low-Density Lipoprotein

“…Among those chemokines, RANTES, MIP-1␣, and MIP-1␤ have been implicated in the formation of atherosclerotic lesions (36). The role of the C-C chemokine MCP-1 in the pathophysiology of atherosclerosis, now recognized as a chronic inflammatory condition, has been demonstrated in humans (16) and animal models of this disease (18,(37)(38)(39)(40). MCP-1 participates in the development of allergic inflammation (12), and is positioned for a similar role in pleurisy.…”