Editorial: Thyroid Hormone—Targeting the Heart

It has long been recognized that thyroid disease states exert profound effects on the heart and cardiovascular system (1, 2). Clinical studies have demonstrated that hyperthyroidism causes enhanced left ventricular systolic and diastolic performance accompanied by an equally important fall in systemic vascular resistance, which together account for the marked increase in cardiac output (3). Basic studies have identified that direct effects of thyroid hormone on the heart can be explained by the ability of triiodothyronine (T3) to regulate the transcription of myocyte specific genes (4, 5). Those genes encode important structural and regulatory proteins including myosin heavy chain isoforms α and β, sarcoplasmic reticulum calcium activated ATPase (SERCA2), phospholamban, theβ -adrenergic receptor, adenylyl cyclase V and VI, and various membrane ion channels (3). This list continues to grow. Predictable increases in heart rate, cardiac contractility, and cardiac mass (hypertrophy) result from chronic thyroid hormone treatment (3). While the effect of thyroid hormone on gene transcription is mediated by T3 binding to discrete nuclear receptors (6), the effect on cardiac mass is indirectly mediated by an increase in cardiac workload (7). Two T3-binding nuclear receptors, TRα1 and TRβ1, are present in the cardiac myocyte. Studies of transgenic animals lacking TRα1 serve to link this receptor isoform with T3-mediated changes in heart rate (8).