Document Detail

Sub-endocardial increase in ROS production affects regional contractile function in ischemic heart failure.
MedLine Citation:
PMID:  22978600     Owner:  NLM     Status:  Publisher    
Aims: Heart failure (HF) is characterized by regionalized contractile alterations resulting in loss of the transmural contractile gradient across the left ventricular free wall. We tested whether a regional alteration in mitochondrial oxidative metabolism during HF could affect myofilament function through PKA signaling. Results: Twelve weeks after permanent left coronary artery ligation that induced myocardial infarction (MI), sub-endocardial (Endo) cardiomyocytes had decreased activity of Complex I and IV of the mitochondrial electron transport chain and produced twice more superoxide anions than sham Endo and sub-epicardial cells. This effect was associated with reduced antioxidant activity of Superoxide Dismutase and Catalase only in MI Endo cells. The myofilament contractile properties (Ca2+ sensitivity and maximal tension), evaluated in skinned cardiomyocytes, were also reduced only in MI Endo myocytes. Conversely, in MI rats treated with the antioxidant N-acetylcysteine (NAC) for 4 weeks, the generation of superoxide anions in Endo cardiomyocytes was normalized and the contractile properties of skinned cardiomyocytes restored. This effect was accompanied by improved in vivo contractility. The beneficial effects of NAC were mediated at least in part through reduction of PKA activity, which was higher in MI myofilaments, particularly the PKA-mediated hyperphosphorylation of cardiac Troponin I. Innovation: Transmural gradient in mitochondrial content/activity is lost during heart failure and mediates ROS-dependent contractile dysfunction. Conclusions: Regionalized alterations in redox signaling affect the contractile machinery of sub-endocardial myocytes through a PKA-dependent pathway that contributes to the loss of the transmural contractile gradient and impairs global contractility.
Lucas Andre; Jérémy Fauconnier; Cyril Reboul; Christine Feillet-Coudray; Pierre Meschin; Charlotte Farah; Gilles Fouret; Sylvain Richard; Alain Lacampagne; Olivier Cazorla
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-9-16
Journal Detail:
Title:  Antioxidants & redox signaling     Volume:  -     ISSN:  1557-7716     ISO Abbreviation:  Antioxid. Redox Signal.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-9-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100888899     Medline TA:  Antioxid Redox Signal     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
INSERM, U1046, Montpellier, France;
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

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

Previous Document:  Sectarianism and the problem of overpopulation: political representations of reproduction in two low...
Next Document:  Multiscale macromolecular simulation: role of evolving ensembles.