The emerging role of TRα1 in cardiac repair: Potential therapeutic implications

Thyroid hormone (TH) is critical for adapting living organisms to environmental stress. Plasma circulating tri-iodothyronine (T3) levels drop in most disease states and are associated with increased oxidative stress. In this context, T3 levels in plasma appear to be an independent determinant for the recovery of cardiac function after myocardial infarction in patients. Thyroid hormone receptor 1 (TR1) seems to be crucial in this response; TR1 accumulates to cell nucleus upon activation of stress induced growth kinase signaling. Furthermore, overexpression of nuclear TR1 in cardiomyocytes can result in pathological or physiological growth (dual action) in absence or presence of its ligand, respectively. Accordingly, inactivation of TR1 receptor prevents reactive hypertrophy after myocardial infarction and results in heart failure with increased phospholamban (PLB) expression and marked activation of p38MAPK. In line with this evidence, TH is shown to limit ischemia/reperfusion injury and convert pathologic to physiologic growth after myocardial infarction via TR1 receptor. TR1 receptor may prove to be a novel pharmacological target for cardiac repair/regeneration therapies. © 2014 Constantinos Pantos and Iordanis Mourouzis.