Document Detail


Absence of myocardial thyroid hormone inactivating deiodinase results in restrictive cardiomyopathy in mice.
MedLine Citation:
PMID:  22403173     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cardiac injury induces myocardial expression of the thyroid hormone inactivating type 3 deiodinase (D3), which in turn dampens local thyroid hormone signaling. Here, we show that the D3 gene (Dio3) is a tissue-specific imprinted gene in the heart, and thus, heterozygous D3 knockout (HtzD3KO) mice constitute a model of cardiac D3 inactivation in an otherwise systemically euthyroid animal. HtzD3KO newborns have normal hearts but later develop restrictive cardiomyopathy due to cardiac-specific increase in thyroid hormone signaling, including myocardial fibrosis, impaired myocardial contractility, and diastolic dysfunction. In wild-type littermates, treatment with isoproterenol-induced myocardial D3 activity and an increase in the left ventricular volumes, typical of cardiac remodeling and dilatation. Remarkably, isoproterenol-treated HtzD3KO mice experienced a further decrease in left ventricular volumes with worsening of the diastolic dysfunction and the restrictive cardiomyopathy, resulting in congestive heart failure and increased mortality. These findings reveal crucial roles for Dio3 in heart function and remodeling, which may have pathophysiologic implications for human restrictive cardiomyopathy.
Authors:
Cintia B Ueta; Behzad N Oskouei; Emerson L Olivares; Jose R Pinto; Mayrin M Correa; Gordana Simovic; Warner S Simonides; Joshua M Hare; Antonio C Bianco
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-03-08
Journal Detail:
Title:  Molecular endocrinology (Baltimore, Md.)     Volume:  26     ISSN:  1944-9917     ISO Abbreviation:  Mol. Endocrinol.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-04-30     Completed Date:  2012-09-10     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  8801431     Medline TA:  Mol Endocrinol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  809-18     Citation Subset:  IM    
Affiliation:
Division of Endocrinology, Diabetes, and Metabolism, University of Miami Miller School of Medicine, Miami, Florida 33136, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Animals, Newborn
Cardiomyopathy, Restrictive / metabolism*,  pathology,  physiopathology
Cardiotonic Agents / administration & dosage,  pharmacology
Dose-Response Relationship, Drug
Gene Expression Profiling
Gene Expression Regulation / drug effects
Heart / drug effects,  growth & development,  physiopathology
Heart Failure / etiology
Infusions, Intravenous
Iodide Peroxidase / genetics,  metabolism*
Isoproterenol / administration & dosage,  pharmacology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Muscle Proteins / genetics,  metabolism
Myocardium / enzymology*,  metabolism,  pathology
RNA, Messenger / metabolism
Ventricular Remodeling
Grant Support
ID/Acronym/Agency:
1K99HL103840-01/HL/NHLBI NIH HHS; 65055//PHS HHS; AG025017/AG/NIA NIH HHS; HL-HL084275/HL/NHLBI NIH HHS; HL065455/HL/NHLBI NIH HHS; HL094849/HL/NHLBI NIH HHS; P20 HL101443/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Cardiotonic Agents; 0/Muscle Proteins; 0/RNA, Messenger; 7683-59-2/Isoproterenol; EC 1.11.1.-/iodothyronine deiodinase type III; EC 1.11.1.8/Iodide Peroxidase
Comments/Corrections

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


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