Document Detail


Cardiomyocyte-specific deletion of gsk3α mitigates post-myocardial infarction remodeling, contractile dysfunction, and heart failure.
MedLine Citation:
PMID:  25125302     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
BACKGROUND: Injury due to myocardial infarction (MI) is largely irreversible. Once an infarct has occurred, the clinical goal becomes limiting remodeling, preserving left ventricular function, and preventing heart failure. Although traditional approaches (e.g., β-blockers) partially preserve left ventricular function, novel strategies are needed to limit ventricular remodeling post-MI.
OBJECTIVES: The aim of this study was to determine the role of glycogen synthase kinase-3α (GSK-3α) in post-MI remodeling.
METHODS: Mice with cardiomyocyte-specific conditional deletion of Gsk3α and littermate controls underwent sham or MI surgery. Heart function was assessed using serial M-mode echocardiography.
RESULTS: Gsk3α deletion in the heart markedly limits remodeling and preserves left ventricular function post-MI. This is due at least in part to dramatic thinning and expansion of the scar in the control hearts, which was less in the heart of knockout (KO) mice. In contrast, the border zone in the KO mice demonstrated a much thicker scar, and there were more viable cardiomyocytes within the scar/border zone. This was associated with less apoptosis and more proliferation of cardiomyocytes in the KO mice. Mechanistically, reduced apoptosis was due, at least in part, to a marked decrease in the Bax/Bcl-2 ratio, and increased cardiomyocyte proliferation was mediated through cyclin E1 and E2F-1 in the hearts of the KO mice.
CONCLUSIONS: Taken together, these findings show that reducing GSK-3α expression in cardiomyocytes limits ventricular remodeling and preserves cardiac function post-MI. Specifically targeting GSK-3α could be a novel strategy to limit adverse remodeling and heart failure.
Authors:
Firdos Ahmad; Hind Lal; Jibin Zhou; Ronald J Vagnozzi; Justine E Yu; Xiying Shang; James R Woodgett; Erhe Gao; Thomas Force
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of the American College of Cardiology     Volume:  64     ISSN:  1558-3597     ISO Abbreviation:  J. Am. Coll. Cardiol.     Publication Date:  2014 Aug 
Date Detail:
Created Date:  2014-08-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8301365     Medline TA:  J Am Coll Cardiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  696-706     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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