Document Detail

Oleylethanolamide activates Ras-Erk pathway and improves myocardial function in doxorubicin-induced heart failure.
MedLine Citation:
PMID:  16269455     Owner:  NLM     Status:  MEDLINE    
Oleylethanolamide (OEA) is a natural fatty acid ethanolamide produced in the heart, but its biological actions in myocardium have not yet been defined. This study was carried out to determine whether OEA could be used to prevent the development of heart failure or improve evolving heart failure. We studied in vivo and in vitro actions of OEA in cardiac muscle. In an animal model of doxorubicin cardiomyopathy, OEA showed robust effects and attenuated the progression of systolic/diastolic dysfunction and ventricular remodeling. During evolving doxorubicin cardiomyopathy, a therapeutic course of OEA treatment partially restored myocardial function. The preventive and therapeutic effects of OEA were associated with significant improvement of survival. To investigate the mechanism of OEA action in cardiac muscle, we have carried out in vitro experiments in cultured cardiomyocytes. The results showed that OEA, through activation of Ras-Raf-1-Mek-Erk signaling, inhibited doxorubicin-induced apoptosis. Additional experiments showed that OEA activation of the Erk pathway involved activation of Neu/ErbB2 receptor, which suggests OEA actions in cardiac muscle might require activation of Neu/ErbB2. In summary, OEA improved ventricular remodeling and augmented cardiac function in doxorubicin cardiomyopathy, possibly involving activation of Neu/ErbB2 and Ras-Erk signaling. These findings suggest OEA is a novel cardioprotective compound that may be used to develop new strategies for the management of cardiomyopathy.
Hou-Fen Su; Ahmad Samsamshariat; Jin Fu; Yue-Xin Shan; Yung-Hsiang Chen; Daniele Piomelli; Ping H Wang
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Publication Detail:
Type:  Comparative Study; Journal Article     Date:  2005-11-03
Journal Detail:
Title:  Endocrinology     Volume:  147     ISSN:  0013-7227     ISO Abbreviation:  Endocrinology     Publication Date:  2006 Feb 
Date Detail:
Created Date:  2006-01-18     Completed Date:  2006-03-10     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  827-34     Citation Subset:  AIM; IM    
Department of Medicine, University of California, Irvine, 92697, USA.
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MeSH Terms
Analysis of Variance
Cardiotonic Agents / metabolism
Disease Models, Animal
Extracellular Signal-Regulated MAP Kinases / metabolism*
Heart Diseases / chemically induced,  metabolism,  prevention & control*
Myocytes, Cardiac / metabolism*
Oleic Acids / metabolism*,  pharmacology
Receptor, erbB-2 / metabolism
Second Messenger Systems / physiology
Signal Transduction / physiology
Ventricular Remodeling / physiology
ras Proteins / metabolism*
Reg. No./Substance:
0/Cardiotonic Agents; 0/Oleic Acids; 0/Oleylethanolamide; 23214-92-8/Doxorubicin; EC, erbB-2; EC Signal-Regulated MAP Kinases; EC Proteins

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