title: 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.
authors.affiliation: Department of Cardiovascular Sciences, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China. wanglih@msu.edu
authors.forename: Li-hong
authors.initials: LH
authors.lastname: Wang
authors.forename: Jun-zhu
authors.initials: JZ
authors.lastname: Chen
authors.forename: Yi-lan
authors.initials: YL
authors.lastname: Sun
authors.forename: Fu-rong
authors.initials: FR
authors.lastname: Zhang
authors.forename: Jian-hua
authors.initials: JH
authors.lastname: Zhu
authors.forename: Shen-jiang
authors.initials: SJ
authors.lastname: Hu
authors.forename: Donna H
authors.initials: DH
authors.lastname: Wang
mesh_terms: 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
chemical_list: D018031:Connexin 43; D017630:Connexins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000097003:Gap Junction alpha-5 Protein