Document Detail


The PGC-1 cascade as a therapeutic target for heart failure.
MedLine Citation:
PMID:  20888832     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The PPARγ coactivator-1 (PGC-1) family of transcriptional coactivators, together with estrogen related receptors (ERRs), plays a key role in regulating genes involved in myocardial fuel metabolism and cardiac function. Increasing evidence implicates dysregulation of this transcriptional regulatory circuit in the metabolic and functional disturbances that presage heart failure due to common diseases such as hypertension and diabetes. Accordingly, the PGC-1/ERR axis is a plausible candidate therapeutic target for novel therapeutics aimed at reversing the energy metabolic disturbances that contribute to heart failure. This review describes the biologic actions of the PGC-1 and ERR cascade and summarizes the evidence that dysregulation of this transcriptional regulatory circuit contributes to heart failure. Potential strategies to modulate this target pathway are reviewed. This article is part of a special issue entitled "Key Signaling Molecules in Hypertrophy and Heart Failure."
Authors:
Joel Schilling; Daniel P Kelly
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review     Date:  2010-10-01
Journal Detail:
Title:  Journal of molecular and cellular cardiology     Volume:  51     ISSN:  1095-8584     ISO Abbreviation:  J. Mol. Cell. Cardiol.     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-09-19     Completed Date:  2012-01-06     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  0262322     Medline TA:  J Mol Cell Cardiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  578-83     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Ltd. All rights reserved.
Affiliation:
Center for Cardiovascular Research, Washington University School of Medicine, St. Louis, MO, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Gene Expression Regulation
Gene Regulatory Networks
Heart / physiopathology
Heart Failure / drug therapy*,  metabolism,  physiopathology
Humans
Molecular Targeted Therapy
Myocardium / metabolism
Receptors, Estrogen / metabolism
Signal Transduction / drug effects*
Transcription Factors / metabolism*
Grant Support
ID/Acronym/Agency:
DK45416/DK/NIDDK NIH HHS; HL058493/HL/NHLBI NIH HHS; K08 HL098373/HL/NHLBI NIH HHS; K08 HL098373-02/HL/NHLBI NIH HHS; K08 HL098373-03/HL/NHLBI NIH HHS; KO8 22-3040-53603//PHS HHS; R01 DK045416-17/DK/NIDDK NIH HHS; R01 HL058493-14/HL/NHLBI NIH HHS; R01 HL101189-03/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Receptors, Estrogen; 0/Transcription Factors; 0/peroxisome-proliferator-activated receptor-gamma coactivator-1
Comments/Corrections

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