Statins reduce connexin40 and connexin43 expression in atherosclerotic aorta of rabbits.
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.
Wang
Li-hong
LH
Department of Cardiovascular Sciences, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China. wanglih@msu.edu
Chen
Jun-zhu
JZ
Sun
Yi-lan
YL
Zhang
Fu-rong
FR
Zhu
Jian-hua
JH
Hu
Shen-jiang
SJ
Wang
Donna H
DH
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism*; D001161:Arteriosclerosis / Q000378:metabolism*; D018031:Connexin 43 / Q000378:metabolism*; D017630:Connexins / Q000378:metabolism*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007150:Immunohistochemistry; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017539:Tunica Intima / Q000378:metabolism; D015854:Up-Regulation; D000097003:Gap Junction alpha-5 Protein
D018031:Connexin 43; D017630:Connexins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000097003:Gap Junction alpha-5 Protein