Characterization of monocyte chemoattractant proteins and CC chemokine receptor 2 expression during atherogenesis in apolipoprotein E-null mice

Aim: we aimed to investigate the expression of monocyte chemoattractant proteins (mcps) and their cognate receptor cc chemokine receptor 2 (ccr2) in aortas of apolipoprotein e-null (apoe -/-) mice during atherogenesis as well as the possible transcription pathway involved in the early induction of mcp-1 in vascular smooth muscle cells (vsmcs) in vivo. methods: atherosclerotic lesion development,aortic mcps and ccr2 mrna expression as well as the cellular localization of mcp-1,ccr2 and mcp-1 related transcription factors in atherosclerotic lesions were analyzed in apoe -/- mice fed a high fat and cholesterol diet. results: mcp-1 and ccr2 mrna expression was significantly induced during early atherogenesis and peaked after 10 and 12 weeks of diet,respectively,whereas mcp-2 and mcp-3 mrna expression elevated in the late phases of lesion development. immunostaining revealed that early mcp-1 expression was localized to vsmcs and that,in advanced lesions,both neointimal vsmcs and intimal macrophages expressed high levels of mcp-1. during the early (0 and 4 weeks of diet) induction of mcp-1 in vsmcs,the regulatory activator protein-1 (ap-1) proteins c-jun and c-fos were highly expressed and observed within the vsmcs nuclei,whereas nuclear factor-κb (nf-κb) protein p65 was only observed within the nuclei of vsmcs after 4 weeks of diet. ccr2 was also identified on intimal macrophages,endothelial cells and vsmcs in advanced lesions. conclusion: this study provides fundamental information on the expression kinetics of mcps and ccr2 during atherogenesis and indicates that the earliest induction of mcp-1 in vsmcs of apoe -/-mice appears to correlate with ap-1 but not nf-κb regulatory pathways.