Thyroid hormone and heart failure: from myocardial protection to systemic regulation

Abstract

Heart failure (HF) is an intriguing model of chronic disease. It starts as an organ disorder developing, in its progression, into a systemic disease in which the dysfunction of other organs plays a relevant clinical and prognostic impact. Furthermore, continuous activation of systemic pathways plays a role in disease progression, switching their effect from protective to harmful. In this combination of organ dysfunction and systemic derangement, thyroid hormone (TH) have an important regulative impact from cardiovascular to systemic level and from molecular/cellular processes to clinical setting. Whether it is accepted to include TH and thyroid stimulating hormone assessment in the clinical HF course, the next challenge will be to ascertain the benefit of TH replacement therapy in HF patients, taking into consideration the type of hormone to administer, dosage and treatment schedule.

Keywords::

• heart failure
• hypothyroidism
• integrin
• low T3 syndrome
• thyroid hormone
• thyroid hormone receptors

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Erratum

Financial & competing interests disclosure

This work was supported by the Tuscany Region Research Grant (DRG 1157/2011). The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Heart failure (HF) is an intriguing model of chronic disease, in which systemic pathways, continuously activated, play a central role in the progression of the disease, switching their effect from protective to harmful.

• An impaired thyroid hormone (TH)–TH receptor axis is a characteristic mark of the failing heart. TRα1, depending on its liganded state, may act as a molecular switch of cellular pathways regulating cardiac regeneration/reparative process, stress response and cardiac remodeling.

• TH non-genomic action depends, at least in part, on interaction of the hormones with specific cell surface or extra-nuclear receptors. Particularly, integrin αVβ3 is present in virtually all cells and mediates a large number of cell signals.

• TH plays a fine cardiovascular and systemic homeostatic role, if we consider the negative impact of mild or overt TH abnormalities in the molecular and cellular processes as experimentally documented, and the negative clinical and prognostic impact in the clinical setting.

• Several questions arising from the clinical scenario support the experimental evidences showing a critical role of TH in HF. These questions include the incidence and prognostic weight of TH abnormalities in HF, the effects of TH abnormalities on the same organs and systems altered in HF and the potential benefits of restoring a normal TH profile by medical replacement therapy.

Notes