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Inhibition of cardiac leptin expression after infarction reduces subsequent dysfunction.
MedLine Citation:
PMID:  20731748     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Leptin is known to exert cardiodepressive effects and to induce left ventricular (LV) remodelling. Nevertheless, the autocrine and/or paracrine activities of this adipokine in the context of post-infarct dysfunction and remodelling have not yet been elucidated. Therefore, we have investigated the evolution of myocardial leptin expression following myocardial infarction (MI) and evaluated the consequences of specific cardiac leptin inhibition on subsequent LV dysfunction. Anaesthetized rats were subjected to temporary coronary occlusion. An antisense oligodesoxynucleotide (AS ODN) directed against leptin mRNA was injected intramyocardially along the border of the infarct 5 days after surgery. Cardiac morphometry and function were monitored by echocardiography over 11 weeks following MI. Production of myocardial leptin and pro-inflammatory cytokines interleukin (IL)-1β and IL-6 were assessed by ELISA. Our results show that (1) cardiac leptin level peaks 7 days after reperfused MI; (2) intramyocardial injection of leptin-AS ODN reduces early IL-1β and IL-6 overexpression and markedly protects contractile function. In conclusion, our findings demonstrate that cardiac leptin expression after MI could contribute to the evolution towards heart failure through autocrine and/or paracrine actions. The detrimental effect of leptin could be mediated by pro-inflammatory cytokines such as IL-1β and IL-6. Our data could constitute the basis of new therapeutic approaches aimed to improve post-MI outcome.
Authors:
C Moro; S Grauzam; O Ormezzano; M C Toufektsian; S Tanguy; P Calabrese; J L Coll; I Bak; B Juhasz; A Tosaki; J de Leiris; F Boucher
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of cellular and molecular medicine     Volume:  15     ISSN:  1582-4934     ISO Abbreviation:  J. Cell. Mol. Med.     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-07-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101083777     Medline TA:  J Cell Mol Med     Country:  England    
Other Details:
Languages:  eng     Pagination:  1688-94     Citation Subset:  IM    
Copyright Information:
© 2011 The Authors Journal compilation © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.
Affiliation:
Laboratoire TIMC-IMAG, UMR 5525 CNRS - University of Grenoble, Grenoble, France Radiopharmaceutiques Biocliniques, INSERM 877, Grenoble, France EA-4278, Université d'Avignon et des Pays de Vaucluse, UFR Sciences, Avignon, France INSERM U823, Institut Albert Bonniot, La Tronche, France University of Debrecen, Debrecen, Hungary.
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