Long-term treatment with eicosapentaenoic acid ameliorates myocardial ischemia-reperfusion injury in pigs in vivo: Involvement of rho-kinase pathway inhibition

Jun Yi Gao, Satoshi Yasuda, Ryuji Tsuburaya, Yoshitaka Ito, Takashi Shiroto, Kiyotaka Hao, Kentaro Aizawa, Yoku Kikuchi, Kenta Ito, Hiroaki Shimokawa

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

Background: Eicosapentaenoic acid (EPA), the major n-3 fatty acid in fish oil, exerts cardioprotective effects against ischemic heart disease; however, the detailed mechanisms remain to be elucidated. Rho-kinase plays an important role in the pathogenesis of cardiovascular diseases including ischemia-reperfusion (I/R) injury. Thus, the hypothesis that long-term EPA treatment ameliorates myocardial I/R injury through Rho-kinase pathway inhibition in pigs in vivo was investigated. Methods and Results: Male pigs were treated with either a control chow or EPA (600 · mg · kg -1 · day -1) for 3 weeks (n=8 each) and were subjected to myocardial ischemia by 90-min occlusion of the left circumflex coronary artery and subsequent 60-min reperfusion. The EPA group had an increased EPA level in red blood cells (4.4±0.3 mol%). The EPA treatment significantly ameliorated myocardial I/R injury, including regional wall motion abnormality (EPA 5.3±3.6 vs. control 35.1±3.8 unit, P<0.0001), left ventricular ejection fraction (EPA 43±9% vs. control 32±7%, P<0.05), occurrence of ventricular arrhythmias (EPA 181±73 vs. control 389±51 events, P<0.0001) and histological accumulation of inflammatory cells (P<0.01). Importantly, the EPA treatment significantly inhibited myocardial Rho-kinase activity (assessed by the extent of the myosin-binding subunit phosphorylation) (EPA 0.47±0.11 vs. control 0.77±0.14, P<0.05) and preserved myocardial eNOS activity (EPA 0.56±0.13 vs. control 0.23±0.07, P<0.01) with a significant correlation noted between them. Conclusions: Long-term treatment with EPA ameliorates I/R injury partly through Rho-kinase pathway inhibition in vivo.

Original languageEnglish
Pages (from-to)1843-1851
Number of pages9
JournalCirculation Journal
Volume75
Issue number8
DOIs
Publication statusPublished - 2011 Aug

Keywords

  • Eicosapentaenoic acid (EPA)
  • Inflammation
  • Nitric oxide
  • Reperfusion

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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