The cardioprotection of simvastatin in reperfused swine hearts relates to the inhibition of myocardial edema by modulating aquaporins via the PKA pathway
International Journal of Cardiology(2013)
摘要
Background and objective
Myocardial edema plays a role in myocardial no-reflow and infarction during ischemia and reperfusion. The effects of statins against no-reflow and infarction may relate to the inhibition of myocardial edema. The current study investigated the role of protein kinase A (PKA) in statin-reduced myocardial edema in reperfused swine hearts.
Methods and results
Minipigs were treated with simvastatin (SIM, 2mg/kg), SIM+H-89 (a PKA inhibitor, 1.0μg/kg/min), or H-89 alone 1h before 90-min ischemia and 3-h reperfusion or sham operation. Ischemia or ischemia–reperfusion induced severe myocardial edema, PKA activation, and up-regulation of aquaporin-1, -4, -8, and ‐9 in the reflow and no-reflow myocardium. SIM pretreatment reduced the sizes of no-reflow and infarct areas by 18.5% and 11.1% (P<0.01), decreased water content in the left ventricle, reflow and no-reflow myocardium by 1.4%, 5.3%, and 4.3% (P<0.05), inhibited cardiomyocytes swelling in the reflow and no-reflow areas by 19.8% and 13.1% (P<0.01), suppressed mitochondrial water accumulation in the reflow and no-reflow areas by 49.0% and 35.9% (P<0.01), increased PKA activity (P<0.01), and blocked the up-regulation of aquaporin-1, -4, -8, and ‐9 in the reflow and no-reflow myocardium. However, these beneficial effects of SIM were partially abolished by inhibiting PKA with H-89.
Conclusions
The cardioprotective effects of acute SIM therapy against myocardial no-reflow and infarction relate to the reduction of myocardial edema by suppressing the expression of aquaporin-1, -4, -8, and ‐9 in a partially PKA-dependent manner.
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关键词
Statins,No-reflow,Ischemia–reperfusion injury,Myocardial edema,Protein kinase A,Aquaporins
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