Effect of pravastatin on ventricular arrhythmias in infarcted rats: Role of connexin43

Chien Chang Chen, Hsiao Yin Lien, Yu Jung Hsu, Chih Chan Lin, Chun Ming Shih, Tsung-Ming Lee

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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 pravastatintreated 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.

Original languageEnglish
Pages (from-to)541-552
Number of pages12
JournalJournal of Applied Physiology
Volume109
Issue number2
DOIs
Publication statusPublished - Aug 2010

Fingerprint

Pravastatin
Connexin 43
Cardiac Arrhythmias
Mevalonic Acid
Endothelin-1
Protein Kinase C
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Sudden Death
Infarction
Electric Stimulation
Fluorescent Antibody Technique
Ligation
Wistar Rats
Real-Time Polymerase Chain Reaction
Epidemiologic Studies
Arteries
Western Blotting
Myocardial Infarction

Keywords

  • Endothelin-1
  • Myocardial infarction

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Medicine(all)

Cite this

Effect of pravastatin on ventricular arrhythmias in infarcted rats : Role of connexin43. / Chen, Chien Chang; Lien, Hsiao Yin; Hsu, Yu Jung; Lin, Chih Chan; Shih, Chun Ming; Lee, Tsung-Ming.

In: Journal of Applied Physiology, Vol. 109, No. 2, 08.2010, p. 541-552.

Research output: Contribution to journalArticle

Chen, Chien Chang ; Lien, Hsiao Yin ; Hsu, Yu Jung ; Lin, Chih Chan ; Shih, Chun Ming ; Lee, Tsung-Ming. / Effect of pravastatin on ventricular arrhythmias in infarcted rats : Role of connexin43. In: Journal of Applied Physiology. 2010 ; Vol. 109, No. 2. pp. 541-552.
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