Document Detail


The cardioprotection of simvastatin in reperfused swine hearts relates to the inhibition of myocardial edema by modulating aquaporins via the PKA pathway.
MedLine Citation:
PMID:  22819122     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
Xiang-Dong Li; Yue-Jin Yang; Yong-Jian Geng; Yu-Tong Cheng; Hai-Tao Zhang; Jing-Lin Zhao; Jin-Qin Yuan; Run-Lin Gao
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-20
Journal Detail:
Title:  International journal of cardiology     Volume:  -     ISSN:  1874-1754     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-7-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8200291     Medline TA:  Int J Cardiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
Affiliation:
Division of Population Genetics and Prevention, State Key Laboratory of Cardiovascular Disease, FUWAI Hospital, National Center for Cardiovascular Diseases,Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
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