Statins reduce connexin40 and connexin43 expression in atherosclerotic aorta of rabbits

Abstract

Background: Gap junction protein connexin43 (Cx43) expression was enhanced in proliferating smooth muscle cells (SMCs) in the neointima of atherosclerotic lesions. HMG-CoA Reductase Inhibitors (statins) can reduce Cx43 expression in vivo and in vitro. Connexin40 (Cx40) is also a very important connexin in SMCs of arterial wall.

Methods: We observed the expression of Cx40 and Cx43 in a rabbit model of a high-cholesterol diet and investigated the effect of lovastatin (10 mg.kg-1.d-1, 2 weeks) or fluvastatin (10 mg.kg-1.d-1, 2 weeks) on these changes by the methods of western blotting, RT-PCR, immunohistochemistry, and transmission electron microscope.

Results: There was abundant expression of Cx40 mRNA and protein in SMCs of rabbit aorta. Besides Cx43, Cx40 expression was also obviously upregulated in atherosclerotic plaques. Treatment with statins reduced the over-expression of Cx43 and Cx40 in atherosclerotic lesion. Cx40 and Cx43 gap junction quantity from each of the arteries obtained at the different drug treatment levels revealed no significant difference. Neointimal SMCs had abundant, large gap junctions, whereas normal SMCs had smaller, less frequent junctions. Statins also normalized the enlarged gap junctions.

Conclusions: These results provide novel in vivo evidence for the key role of gap junctions in atherogenesis and the possible mechanism in antiatherogenic effect of statins.