Simvastatin reduces Connexin43 expression and inhibits rabbit atherosclerotic lesion formation

    LI Jianª²Jun£¬ LIN Hong£¬ LI Zhuª²Yi£¬ LI Hongª²Zeng

    Department of Neurology, Tangdu Hospital, Fourth Military Medical University, Xi¬ðan 710038, China

    ¡¾Abstract¡¿ AIM: To demonstrate that simvastatin can influence atherosclerotic plaque formation and stability by decreasing the expression of gap junction protein connexin43 (Cx43) in atherosclerotic lesions. METHODS: The role of Cx43 in atherogenesis was examined by a pharmacological approach. The rabbit model of atherogenesis was established by a highª²cholesterol diet. The expression of connexin 43 and macrophages in vivo was determined by immunohistochemistry and the expression of connexin 43 in cultured smooth muscle cells was determined with Western blot. The quantity of connexin43 expression was analyzed with computer images. RESULTS: We observed that HMGª²CoA reductase inhibitors, or "statins", lipidª²lowering drugs well known for their pleiotropic antiatherogenic effects, reduced Cx43 expression in primary human vascular cells in vitro. Atheroma of rabbits orally treated with simvastatin contained fewer inflammatory cells and exhibited thicker fibrous caps than controls, which was associated with reduced Cx43 expression in lesions of statinª²treated rabbits. CONCLUSION: These data indicate the critical role of Cx43ª²mediated gap junctional communication in atherosclerotic plaque formation. Reduced Cx43ª²mediated intercellular communication leads to changes in atherogenesis. These findings show that Cx43ª²mediated intercellular communication can be used as a new potential therapeutic target in atherogenesis. ......