TY - JOUR
T1 - Long-term treatment with eicosapentaenoic acid ameliorates myocardial ischemia-reperfusion injury in pigs in vivo
T2 - Involvement of rho-kinase pathway inhibition
AU - Gao, Jun Yi
AU - Yasuda, Satoshi
AU - Tsuburaya, Ryuji
AU - Ito, Yoshitaka
AU - Shiroto, Takashi
AU - Hao, Kiyotaka
AU - Aizawa, Kentaro
AU - Kikuchi, Yoku
AU - Ito, Kenta
AU - Shimokawa, Hiroaki
N1 - Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2011/8
Y1 - 2011/8
N2 - 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.
AB - 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.
KW - Eicosapentaenoic acid (EPA)
KW - Inflammation
KW - Nitric oxide
KW - Reperfusion
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U2 - 10.1253/circj.CJ-11-0209
DO - 10.1253/circj.CJ-11-0209
M3 - Article
C2 - 21628831
AN - SCOPUS:79960790541
VL - 75
SP - 1843
EP - 1851
JO - Circulation Journal
JF - Circulation Journal
SN - 1346-9843
IS - 8
ER -