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Absence of Myocardial Thyroid Hormone Inactivating Deiodinase Results in Restrictive Cardiomyopathy in Mice

Title: Absence of Myocardial Thyroid Hormone Inactivating Deiodinase Results in Restrictive Cardiomyopathy in Mice.
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Name(s): Ueta, Cintia, author
Oskouei, Behzad, author
Olivares, Emerson, author
Pinto, Jose, author
Correa, Mayrin, author
Simovic, Gordana, author
Simonides, Warner, author
Hare, Joshua, author
Bianco, Antônio Carlos, author
Type of Resource: text
Genre: Text
Issuance: serial
Date Issued: 2012
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: 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.
Identifier: FSU_migr_biomed_faculty_publications-0052 (IID), 10.1210/me.2011-1325 (DOI)
Keywords: cardiomyopathy, cardiotonic agents, dose-response relationship, gene expression profiling, gene expression regulation, heart, heart failure, infusions, intravenous, iodide peroxidase, isoproterenol, mice, inbred C57BL, muscle proteins, myocardium, RNA messenger, ventricular remodeling
Uncontrolled subjects: Animals, Animals, Newborn, Cardiomyopathy, Restrictive, Cardiotonic Agents, Dose-Response Relationship, Drug, Gene Expression Profiling, Gene Expression Regulation, Heart, Heart Failure, Infusions, Intravenous, Iodide Peroxidase, Isoproterenol, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Muscle Proteins, Myocardium, RNA, Messenger, Ventricular Remodeling
Note: Originally published in Molecular'>http://press.endocrine.org/doi/abs/10.1210/me.2011-1325">Molecular Endocrinology.
Citation: Ueta CB, Oskouei BN, Olivares EL, Pinto JR, Correa MM, Simovic G, Simonides WS, Hare JM, Bianco AC. (2012). Absence of myocardial thyroid hormone inactivating deiodinase results in restrictive cardiomyopathy in mice. Mol Endocrinol, 26(5):809-18. doi: 10.1210/me.2011-1325.
Subject(s): Amino acids
Peptides
Proteins
Diagnosis, Laboratory -- Equipment and supplies
Therapeutics
Cardiovascular system -- Diseases
Cardiovascular system
Chemicals -- Physiological effect
Chemicals
Drugs
Coenzymes
Enzymes
Genetics
Medical sciences
Musculoskeletal system
Nucleic acids
Nucleosides
Organic compounds
Pathology
Symptoms
Links: http://dx.doi.org/10.1210/me.2011-1325
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_migr_biomed_faculty_publications-0052
Owner Institution: FSU
Is Part of Series: Department of Biomedical Sciences Faculty Publications.
Is Part Of: Molecular Endocrinology.
Issue: 5, 26

Choose the citation style.
Ueta, C., Oskouei, B., Olivares, E., Pinto, J., Correa, M., Simovic, G., … Bianco, A. C. (2012). Absence of Myocardial Thyroid Hormone Inactivating Deiodinase Results in Restrictive Cardiomyopathy in Mice. Molecular Endocrinology. Retrieved from http://dx.doi.org/10.1210/me.2011-1325