Cardiac thyroid-hormone deiodinative pathways in ventricular hypertrophy and heart failure

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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.

Original languageEnglish
Title of host publicationThyroid and Heart Failure
Subtitle of host publicationFrom Pathophysiology to Clinics
PublisherSpringer Milan
Number of pages11
ISBN (Print)9788847011427
Publication statusPublished - 2009


  • Deiodinase type 1 (D1)
  • Deiodinase type 2 (D2)
  • Deiodinase type 3 (D3)
  • Heart failure
  • Hypothyroid
  • Hypoxia
  • Hypoxia-inducible factor 1 α subunit (HIF-1α)
  • Pulmonary arterial hypertension
  • Thyroid hormone
  • Transforming growth factor-β (TGFβ)
  • Triiodothyronine (T)
  • Ventricular hypertrophy

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