Document Detail


Mitochondria selective S-nitrosation by mitochondria-targeted S-nitrosothiol protects against post-infarct heart failure in mouse hearts.
MedLine Citation:
PMID:  24891297     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
AIMS: Recently it has been shown that the mitochondria-targeted S-nitrosothiol MitoSNO protects against acute ischaemia/reperfusion (IR) injury by inhibiting the reactivation of mitochondrial complex I in the first minutes of reperfusion of ischaemic tissue, thereby preventing free radical formation that underlies IR injury. However, it remains unclear how this transient inhibition of mitochondrial complex I-mediated free radicals at reperfusion affects the long-term recovery of the heart following IR injury. Here we determined whether the acute protection by MitoSNO at reperfusion prevented the subsequent development of post-myocardial infarction heart failure.
METHODS AND RESULTS: Mice were subjected to 30 min left coronary artery occlusion followed by reperfusion and recovery over 28 days. MitoSNO (100 ng/kg) was applied 5 min before the onset of reperfusion followed by 20 min infusion (1 ng/kg/min). Infarct size and cardiac function were measured by magnetic resonance imaging (MRI) 24 h after infarction. MitoSNO-treated mice exhibited reduced infarct size and preserved function. In addition, MitoSNO at reperfusion improved outcome measures 28 days post-IR, including preserved systolic function (63.7 ±1.8% LVEF vs. 53.7 ± 2.1% in controls, P = 0.01) and tissue fibrosis.
CONCLUSIONS: MitoSNO action acutely at reperfusion reduces infarct size and protects from post-myocardial infarction heart failure. Therefore, targeted inhibition of mitochondrial complex I in the first minutes of reperfusion by MitoSNO is a rational therapeutic strategy for preventing subsequent heart failure in patients undergoing IR injury.
Authors:
Carmen Methner; Edward T Chouchani; Guido Buonincontri; Victoria R Pell; Stephen J Sawiak; Michael P Murphy; Thomas Krieg
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2014-05-31
Journal Detail:
Title:  European journal of heart failure     Volume:  16     ISSN:  1879-0844     ISO Abbreviation:  Eur. J. Heart Fail.     Publication Date:  2014 Jul 
Date Detail:
Created Date:  2014-07-03     Completed Date:  -     Revised Date:  2014-12-09    
Medline Journal Info:
Nlm Unique ID:  100887595     Medline TA:  Eur J Heart Fail     Country:  England    
Other Details:
Languages:  eng     Pagination:  712-7     Citation Subset:  IM    
Copyright Information:
© 2014 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
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MeSH Terms
Descriptor/Qualifier:
Grant Support
ID/Acronym/Agency:
//British Heart Foundation; //Medical Research Council

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