Document Detail

Effect of pravastatin on ventricular arrhythmias in infarcted rats: role of connexin43.
MedLine Citation:
PMID:  20466804     Owner:  NLM     Status:  In-Process    
Epidemiologic studies showed that men treated with statins appear to have a lower incidence of sudden death than men without statins. However, the specific factor for this remained disappointingly elusive. We assessed whether pravastatin enhanced connexin43 expression after myocardial infarction through attenuation of endothelin-1. Twenty-four hours after ligation of the anterior descending artery, male Wistar rats were randomized to vehicle, pravastatin, mevalonate, bosentan, or a combination of pravastatin and mevalonate or pravastatin and bosentan for 4 wk. Myocardial endothelin-1 levels were significantly elevated in vehicle-treated rats at the border zone compared with sham-operated rats. Myocardial connexin43 expression at the border zone was significantly decreased in vehicle-treated infarcted rats compared with sham-operated rats. Attenuated connexin43 expression was blunted after administration of pravastatin, as assessed by immunofluorescence analysis, Western blotting, and real-time quantitative RT-PCR of connexin43. Bosentan enhanced connexin43 amount in infarcted rats and did not have additional beneficial effects on pravastatin-treated rats. Arrhythmic scores during programmed stimulation in vehicle-treated rats were significantly higher than scores in those treated with pravastatin. In contrast, the beneficial effects of pravastatin-induced connexin43 were abolished by the addition of mevalonate and a protein kinase C inducer. In addition, the amount of connexin43 showed significant increase after addition of bisindolylmaleimide, implicating that protein kinase C is a relevant target in endothelin-1-mediated connexin43 expression. Thus chronic use of pravastatin after infarction, resulting in enhanced connexin43 amount by attenuation of mevalonate-dependent endothelin-1 through a protein kinase C-dependent pathway, may attenuate the arrhythmogenic response to programmed electrical stimulation.
Chien-Chang Chen; Hsiao-Yin Lien; Yu-Jung Hsu; Chih-Chan Lin; Chun-Ming Shih; Tsung-Ming Lee
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-05-13
Journal Detail:
Title:  Journal of applied physiology (Bethesda, Md. : 1985)     Volume:  109     ISSN:  1522-1601     ISO Abbreviation:  J. Appl. Physiol.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-08-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8502536     Medline TA:  J Appl Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  541-52     Citation Subset:  IM    
Department of Cosmetic Science, Chia Nan University of Pharmacy Science, Tainan, Taiwan.
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