Document Detail

Cardiac myocyte follistatin-like 1 functions to attenuate hypertrophy following pressure overload.
MedLine Citation:
PMID:  21987816     Owner:  NLM     Status:  MEDLINE    
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.
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
Related Documents :
21194056 - Rotational atherectomy to facilitate stent expansion after deployment in st-segment-ele...
21185676 - Aluminium-induced ventricular tachycardia.
22814936 - Aldehyde dehydrogenase-2 activation during cardioplegic arrest enhances the cardioprote...
857356 - Changes in left ventricular activity during apnea and face immersion.
2476736 - Iliac vein approach to permanent pacemaker implantation.
9710726 - Lymph isolated from a regional scald injury produces a negative inotropic effect in dogs.
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    
Whitaker Cardiovascular Institute, Boston University, Boston, MA 02118, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Analysis of Variance
Blotting, Western
Cardiomegaly / metabolism*
DNA Primers / genetics
Follistatin-Related Proteins / genetics,  metabolism*
Mice, Knockout
Myocytes, Cardiac / metabolism*
Real-Time Polymerase Chain Reaction
Signal Transduction / physiology
Statistics, Nonparametric
Ventricular Remodeling / genetics,  physiology*
Grant Support
Reg. No./Substance:
0/DNA Primers; 0/Follistatin-Related Proteins; 0/Fstl1 protein, mouse

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

Previous Document:  Direct activation of antigen-presenting cells is required for CD8+ T-cell priming and tumor vaccinat...
Next Document:  Sexual selection by female immunity against paternal antigens can fix loss of function alleles.