Document Detail


Cardiac myocyte follistatin-like 1 functions to attenuate hypertrophy following pressure overload.
MedLine Citation:
PMID:  21987816     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Factors secreted by the heart, referred to as "cardiokines," have diverse actions in the maintenance of cardiac homeostasis and remodeling. Follistatin-like 1 (Fstl1) is a secreted glycoprotein expressed in the adult heart and is induced in response to injurious conditions that promote myocardial hypertrophy and heart failure. The aim of this study was to investigate the role of cardiac Fstl1 in the remodeling response to pressure overload. Cardiac myocyte-specific Fstl1-KO mice were constructed and subjected to pressure overload induced by transverse aortic constriction (TAC). Although Fstl1-KO mice displayed no detectable baseline phenotype, TAC led to enhanced cardiac hypertrophic growth and a pronounced loss in ventricular performance by 4 wk compared with control mice. Conversely, mice that acutely or chronically overexpressed Fstl1 were resistant to pressure overload-induced hypertrophy and cardiac failure. Fstl1-deficient mice displayed a reduction in TAC-induced AMP-activated protein kinase (AMPK) activation in heart, whereas Fstl1 overexpression led to increased myocardial AMPK activation under these conditions. In cultured neonatal cardiomyocytes, administration of Fstl1 promoted AMPK activation and antagonized phenylephrine-induced hypertrophy. Inhibition of AMPK attenuated the antihypertrophic effect of Fstl1 treatment. These results document that cardiac Fstl1 functions as an autocrine/paracrine regulatory factor that antagonizes myocyte hypertrophic growth and the loss of ventricular performance in response to pressure overload, possibly through a mechanism involving the activation of the AMPK signaling axis.
Authors:
Masayuki Shimano; Noriyuki Ouchi; Kazuto Nakamura; Bram van Wijk; Koji Ohashi; Yasuhide Asaumi; Akiko Higuchi; David R Pimentel; Flora Sam; Toyoaki Murohara; Maurice J B van den Hoff; Kenneth Walsh
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-10-10
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  108     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-10-26     Completed Date:  2011-12-19     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E899-906     Citation Subset:  IM    
Affiliation:
Whitaker Cardiovascular Institute, Boston University, Boston, MA 02118, USA.
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MeSH Terms
Descriptor/Qualifier:
Analysis of Variance
Animals
Blotting, Western
Cardiomegaly / metabolism*
DNA Primers / genetics
Echocardiography
Follistatin-Related Proteins / genetics,  metabolism*
Mice
Mice, Knockout
Myocytes, Cardiac / metabolism*
Pressure
Real-Time Polymerase Chain Reaction
Signal Transduction / physiology
Statistics, Nonparametric
Ventricular Remodeling / genetics,  physiology*
Grant Support
ID/Acronym/Agency:
AG15052/AG/NIA NIH HHS; AG34972/AG/NIA NIH HHS; HL102874/HL/NHLBI NIH HHS; HL68758/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/DNA Primers; 0/Follistatin-Related Proteins; 0/Fstl1 protein, mouse
Comments/Corrections

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


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