Document Detail


Role of adenosine A2B receptor signaling in contribution of cardiac mesenchymal stem-like cells to myocardial scar formation.
MedLine Citation:
PMID:  24584483     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Adenosine levels increase in ischemic hearts and contribute to the modulation of that pathological environment. We previously showed that A2B adenosine receptors on mouse cardiac Sca1(+)CD31(-) mesenchymal stromal cells upregulate secretion of paracrine factors that may contribute to the improvement in cardiac recovery seen when these cells are transplanted in infarcted hearts. In this study, we tested the hypothesis that A2B receptor signaling regulates the transition of Sca1(+)CD31(-) cells, which occurs after myocardial injury, into a myofibroblast phenotype that promotes myocardial repair and remodeling. In vitro, TGFβ1 induced the expression of the myofibroblast marker α-smooth muscle actin (αSMA) and increased collagen I generation in Sca1(+)CD31(-) cells. Stimulation of A2B receptors attenuated TGFβ1-induced collagen I secretion but had no effect on αSMA expression. In vivo, myocardial infarction resulted in a rapid increase in the numbers of αSMA-positive cardiac stromal cells by day 5 followed by a gradual decline. Genetic deletion of A2B receptors had no effect on the initial accumulation of αSMA-expressing stromal cells but hastened their subsequent decline; the numbers of αSMA-positive cells including Sca1(+)CD31(-) cells remained significantly higher in wild type compared with A2B knockout hearts. Thus, our study revealed a significant contribution of cardiac Sca1(+)CD31(-) cells to the accumulation of αSMA-expressing cells after infarction and implicated A2B receptor signaling in regulation of myocardial repair and remodeling by delaying deactivation of these cells. It is plausible that this phenomenon may contribute to the beneficial effects of transplantation of these cells to the injured heart.
Authors:
Sergey Ryzhov; Bong Hwan Sung; Qinkun Zhang; Alissa Weaver; Richard J Gumina; Italo Biaggioni; Igor Feoktistov
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-3-1
Journal Detail:
Title:  Purinergic signalling     Volume:  -     ISSN:  1573-9546     ISO Abbreviation:  Purinergic Signal.     Publication Date:  2014 Mar 
Date Detail:
Created Date:  2014-3-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101250499     Medline TA:  Purinergic Signal     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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