Translational potential of thyroid hormone and its analogs

Thyroid hormone has unique properties affecting the heart, and the vasculature and cholesterol metabolism. There is interest in using thyromimetic agents as possible treatment options for heart failure based on data demonstrating the ability of these agents to improve systolic and diastolic left ventricular function as well as their vasodilatory action. The inverse relationship between heart failure severity and serum triiodothyronine (T3) levels has also been interpreted by some as an indication that thyroid hormone therapy might be useful. In the 1950s, investigators began developing thyroid hormone analogs that could lower cholesterol, that selectively bind to β1-type nuclear thyroid hormone receptors (TR), which are responsible for cholesterol-lowering activity, without activating α1-type receptors in the heart. The identification of 3,5-diiodothyropropionic acid (DITPA) that binds to both α- and β-type TRs with relatively low affinity was unique in that this analog improves left ventricular function in heart failure as well as lowers cholesterol. The aim of this review is to summarize information known about the interactions between thyroid hormones and the cardiovascular system, and the potential therapeutic effects of thyroid analogs in chronic heart disease. This article is part of a special issue entitled "Key Signaling Molecules in Hypertrophy and Heart Failure."