title: The emerging role of TRα1 in cardiac repair: potential therapeutic implications.
abstract: 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 α1 (TRα1) seems to be crucial in this response; TRα1 accumulates to cell nucleus upon activation of stress induced growth kinase signaling. Furthermore, overexpression of nuclear TRα1 in cardiomyocytes can result in pathological or physiological growth (dual action) in absence or presence of its ligand, respectively. Accordingly, inactivation of TRα1 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 TRα1 receptor. TRα1 receptor may prove to be a novel pharmacological target for cardiac repair/regeneration therapies.
authors.affiliation: Department of Pharmacology, University of Athens, 75 Mikras Asias Avenue, Goudi, 11527 Athens, Greece.
authors.forename: Constantinos
authors.identifier: 0000-0003-2449-0991
authors.initials: C
authors.lastname: Pantos
authors.affiliation: Department of Pharmacology, University of Athens, 75 Mikras Asias Avenue, Goudi, 11527 Athens, Greece.
authors.forename: Iordanis
authors.initials: I
authors.lastname: Mourouzis
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects; D000818:Animals; D006801:Humans; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D013312:Stress, Physiological / Q000187:drug effects; D037021:Thyroid Hormone Receptors alpha / Q000378:metabolism*; D013963:Thyroid Hormones / Q000494:pharmacology / Q000627:therapeutic use*; D014945:Wound Healing / Q000187:drug effects
chemical_list: D037021:Thyroid Hormone Receptors alpha; D013963:Thyroid Hormones