Document Detail


Cardiac-specific mindin overexpression attenuates cardiac hypertrophy via blocking AKT/GSK3β and TGF-β1-Smad signalling.
MedLine Citation:
PMID:  21632881     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
AIMS: Mindin is a secreted extracellular matrix protein, an integrin ligand, and an angiogenesis inhibitor, other examples of which are all key players in the progression of cardiac hypertrophy. However, its function during cardiac hypertrophy remains unclear. This study was aimed to identify the effect of mindin on cardiac hypertrophy and the underlying mechanisms.
METHODS AND RESULTS: A significant down-regulation of mindin expression was observed in human failing hearts. To further investigate the role of mindin in cardiac hypertrophy, we used cultured neonatal rat cardiomyocytes with gain and loss of mindin function and cardiac-specific Mindin-overexpressing transgenic (TG) mice. In cultured cardiomyocytes, mindin negatively regulated angiotensin II (Ang II)-mediated hypertrophic growth, as detected by [(3)H]-Leucine incorporation, cardiac myocyte area, and hypertrophic marker protein levels. Cardiac hypertrophy in vivo was produced by aortic banding (AB) or Ang II infusion in TG mice and their wild-type controls. The extent of cardiac hypertrophy was evaluated by echocardiography as well as by pathological and molecular analyses of heart samples. Mindin overexpression in the heart markedly attenuated cardiac hypertrophy, fibrosis, and left ventricular dysfunction in mice in response to AB or Ang II. Further analysis of the signalling events in vitro and in vivo indicated that these beneficial effects of mindin were associated with the interruption of AKT/glycogen synthase kinase 3β (GSK3β) and transforming growth factor (TGF)-β1-Smad signalling.
CONCLUSION: The present study demonstrates for the first time that mindin serves as a novel mediator that protects against cardiac hypertrophy and the transition to heart failure by blocking AKT/GSK3β and TGF-β1-Smad signalling.
Authors:
Ling Yan; Xiang Wei; Qi-Zhu Tang; Jinghua Feng; Yan Zhang; Chen Liu; Zhou-Yan Bian; Lian-Feng Zhang; Manyin Chen; Xue Bai; Ai-Bing Wang; John Fassett; Yingjie Chen; You-Wen He; Qinglin Yang; Peter P Liu; Hongliang Li
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-06-01
Journal Detail:
Title:  Cardiovascular research     Volume:  92     ISSN:  1755-3245     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-09-15     Completed Date:  2012-01-23     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  85-94     Citation Subset:  IM    
Affiliation:
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cardiomegaly / prevention & control*
Echocardiography
Extracellular Matrix Proteins / physiology*
Fibrosis
Forkhead Transcription Factors / antagonists & inhibitors
Glycogen Synthase Kinase 3 / antagonists & inhibitors*
Hemodynamics
Humans
Male
Mice
Mice, Inbred C57BL
Myocardium / pathology
Phosphorylation
Proto-Oncogene Proteins c-akt / antagonists & inhibitors*
Rats
Rats, Sprague-Dawley
Signal Transduction / physiology*
Smad Proteins / antagonists & inhibitors*,  physiology
TOR Serine-Threonine Kinases / antagonists & inhibitors
Transforming Growth Factor beta1 / antagonists & inhibitors*,  physiology
Grant Support
ID/Acronym/Agency:
R01 HL084456/HL/NHLBI NIH HHS; R01 HL085499/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Extracellular Matrix Proteins; 0/Forkhead Transcription Factors; 0/Foxo1 protein, mouse; 0/Smad Proteins; 0/Transforming Growth Factor beta1; 0/mindin; EC 2.7.1.1/TOR Serine-Threonine Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.1/glycogen synthase kinase 3 beta; EC 2.7.11.26/Glycogen Synthase Kinase 3
Comments/Corrections

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