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Cardiac Thyroid-Hormone Deiodinative Pathways in Ventricular Hypertrophy and Heart Failure

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Thyroid and Heart Failure

Abstract

Many of the cardiac genes that are involved in contractile dysfunction following pathological ventricular remodeling are transcriptionally regulated by thyroid hormone (TH). The phenotype of the pathologically hypertrophied cardiomyocyte suggests that reduced TH signaling contributes to its development. Increased expression of the TH-degrading enzyme deiodinase type 3 (D3) in cardiomyocytes of hypertrophic left or right ventricles has recently been described for different rodent models of heart failure. At least in right ventricular failure, this was associated with a severe, cardiomyocyte-specific hypothyroid condition. D3 expression is transcriptionally stimulated by factors that are implicated in cardiomyocyte hypertrophy, e.g., mitogen-activated protein kinases (MAPK) ERK, and p38 and Smad proteins activated by transforming growth factor-β (TGFβ). Hypoxia-inducible factor 1 (HIF-1) also stimulates D3 transcription. Reduced oxygen tension and subsequent HIF-1 signaling may occur in the hypertrophic cardiomyocyte, and this appears to account for the increased D3 expression in the model of right ventricular failure. It remains to be established whether stimulation of D3 activity and the ensuing local hypothyroid condition with reduction of energy turnover are an adaptive response or contribute to the further deterioration of contractile function and heart failure.

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Authors and Affiliations

  1. Institute for Cardiovascular Research Department of Physiology, VU University Medical Center Amsterdam, Amsterdam, The Netherlands

    Warner S. Simonides PhD

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  1. Warner S. Simonides PhD
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Editors and Affiliations

  1. C.N.R. Clinical Physiology Institute, S. Cataldo Research Campus, Pisa, Italy

    Giorgio Iervasi  & Alessandro Pingitore  & 

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Simonides, W.S. (2009). Cardiac Thyroid-Hormone Deiodinative Pathways in Ventricular Hypertrophy and Heart Failure. In: Iervasi, G., Pingitore, A. (eds) Thyroid and Heart Failure. Springer, Milano. https://doi.org/10.1007/978-88-470-1143-4_7

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  • DOI: https://doi.org/10.1007/978-88-470-1143-4_7

  • Publisher Name: Springer, Milano

  • Print ISBN: 978-88-470-1142-7

  • Online ISBN: 978-88-470-1143-4

  • eBook Packages: MedicineMedicine (R0)

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