Heart Failure Reviews

, Volume 15, Issue 2, pp 121-124

First online:

Open Access This content is freely available online to anyone, anywhere at any time.

The role of thyroid hormone nuclear receptors in the heart: evidence from pharmacological approaches

  • Wilmar M. WiersingaAffiliated withDepartment of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam Email author 


This review evaluates the hypothesis that the cardiac effects of amiodarone can be explained—at least partly—by the induction of a local ‘hypothyroid-like condition’ in the heart. Evidence supporting the hypothesis comprises the observation that amiodarone exerts an inhibitory effect on the binding of T3 to thyroid hormone receptors (TR) alpha-1 and beta-1 in vitro, and on the expression of particular T3-dependent genes in vivo. In the heart, amiodarone decreases heart rate and alpha myosin heavy chain expression (mediated via TR alpha-1), and increases sarcoplasmic reticulum calcium-activated ATPase and beta myosin heavy chain expression (mediated via TR beta-1). Recent data show a significant similarity in expression profiles of 8,435 genes in the heart of hypothyroid and amiodarone-treated animals, although similarities do not always exist in transcripts of ion channel genes. Induction of a hypothyroid cardiac phenotype by amiodarone may be advantageous by decreasing energy demands and increasing energy availability.


Amiodarone Dronedarone Hypothyroidism Thyroid hormone receptor alpha-1 Thyroid hormone receptor beta-1 Heart rate Alpha MHC Beta MHC SERCA2a