Document Detail


Regulation and actions of activin A and follistatin in myocardial ischaemia-reperfusion injury.
MedLine Citation:
PMID:  25052838     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Activin A, a member of the transforming growth factor-β superfamily, is stimulated early in inflammation via the Toll-like receptor (TLR) 4 signalling pathway, which is also activated in myocardial ischaemia-reperfusion. Neutralising activin A by treatment with the activin-binding protein, follistatin, reduces inflammation and mortality in several disease models. This study assesses the regulation of activin A and follistatin in a murine myocardial ischaemia-reperfusion model and determines whether exogenous follistatin treatment is protective against injury. Myocardial activin A and follistatin protein levels were elevated following 30min of ischaemia and 2h of reperfusion in wild-type mice. Activin A, but not follistatin, gene expression was also up-regulated. Serum activin A did not change significantly, but serum follistatin decreased. These responses to ischaemia-reperfusion were absent in TLR4(-/-) mice. Pre-treatment with follistatin significantly reduced ischaemia-reperfusion induced myocardial infarction. In mouse neonatal cardiomyocyte cultures, activin A exacerbated, while follistatin reduced, cellular injury after 3h of hypoxia and 2h of re-oxygenation. Neither activin A nor follistatin affected hypoxia-reoxygenation induced reactive oxygen species production by these cells. However, activin A reduced cardiomyocyte mitochondrial membrane potential, and follistatin treatment ameliorated the effect of hypoxia-reoxygenation on cardiomyocyte mitochondrial membrane potential. Taken together, these data indicate that myocardial ischaemia-reperfusion, through activation of TLR4 signalling, stimulates local production of activin A, which damages cardiomyocytes independently of increased reactive oxygen species. Blocking activin action by exogenous follistatin reduces this damage.
Authors:
Yi Chen; Christine Rothnie; Denise Spring; Edward Verrier; Kylie Venardos; David Kaye; David J Phillips; Mark P Hedger; Julian A Smith
Related Documents :
24067598 - Myocardial protection by co-administration of l-arginine and tetrahydrobiopterin during...
15477418 - Electromechanical mapping identifies improvement in function and retention of contracti...
21801598 - Preliminary experience with the use of self-expanding stent as a thrombectomy device in...
10399998 - Pravastatin prevents clinical events in revascularized patients with average cholestero...
16146018 - Cardiac arrest in the early stage of cardiosurgical procedure.
23967378 - Aav-mediated gene therapy for heart failure: enhancing contractility and calcium handling.
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-7-19
Journal Detail:
Title:  Cytokine     Volume:  -     ISSN:  1096-0023     ISO Abbreviation:  Cytokine     Publication Date:  2014 Jul 
Date Detail:
Created Date:  2014-7-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9005353     Medline TA:  Cytokine     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014 Elsevier Ltd. All rights reserved.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Bone mechanobiology, gravity and tissue engineering: effects and insights.
Next Document:  Amitriptyline and bromazepam in the treatment of vibratory angioedema: which role for neuroinflammat...