Document Detail


Induction of MicroRNA-21 with Exogenous Hydrogen Sulfide Attenuates Myocardial Ischemic and Inflammatory Injury in Mice.
MedLine Citation:
PMID:  24825878     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND: -Maintaining physiological levels of hydrogen sulfide (H2S) during ischemia is necessary to limit injury to the heart. Due to the anti-inflammatory effects of H2S, we proposed that the H2S donor, Na2S, would attenuate myocardial injury through upregulation of 'protective' microRNA (miR)-21 and suppression of the inflammasome, a macromolecular structure that amplifies inflammation and mediates further injury.
METHODS AND RESULTS: -Na2S-induced miR-21 expression was measured by qPCR in adult primary rat cardiomyocytes and in the mouse heart. We measured inflammasome formation and activity in cardiomyocytes challenged with lipopolysaccharide (LPS) and adenosine-tri-phosphate (ATP) or simulated ischemia/reoxygenation; and in the heart following regional myocardial ischemia/reperfusion (I/R), in the presence or absence of Na2S. To assess the direct anti-inflammatory effects of H2S in vivo, we utilized a peritonitis model by way of intraperitoneal injection of zymosan A. Na2S attenuated inflammasome formation and activity - measured by counting cytoplasmic aggregates of the scaffold protein Apoptosis Speck-like protein containing a Caspase-recruitment domain (ASC; -57%) and caspase-1 activity (-50%) in isolated cardiomyocytes and in the mouse heart (all P<0.05). Na2S also inhibited apoptosis (-38%) and necrosis (-43%) in cardiomyocytes in vitro and reduced myocardial infarct size (-63%) following I/R injury in vivo (all P<0.05). These protective effects were absent in cells treated with antagomiR-21 and in miR-21 KO mice. Na2S also limited the severity of inflammasome-dependent inflammation in the model of peritonitis (P<0.05) in wild-type but not in miR-21 KO mice.
CONCLUSIONS: -Na2S induces cardioprotective effects through miR-21-dependent attenuation of ischemic and inflammatory injury in cardiomyocytes.
Authors:
Stefano Toldo; Anindita Das; Eleonora Mezzaroma; Vinh Q Chau; Carlo Marchetti; David Durrant; Arun Samidurai; Benjamin W Van Tassell; Chang Yin; Ramzi A Ockaili; Navin Vigneshwar; Nitai D Mukhopadhyay; Rakesh C Kukreja; Antonio Abbate; Fadi N Salloum
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-5-13
Journal Detail:
Title:  Circulation. Cardiovascular genetics     Volume:  -     ISSN:  1942-3268     ISO Abbreviation:  Circ Cardiovasc Genet     Publication Date:  2014 May 
Date Detail:
Created Date:  2014-5-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101489144     Medline TA:  Circ Cardiovasc Genet     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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