Triiodothyronine Prevents Cardiac Ischemia/Reperfusion Mitochondrial Impairment and Cell Loss by Regulating miR30a/p53 Axis

• DOI: 10.1210/en.2014-1106
• Publication Date: 2014-08-19T15:03:13Z
• Authors: Francesca Forini; Claudia Kusmic; Giuseppina Nicolini; Laura Mariani; Riccardo Zucchi; Marco Matteucci; Giorgio Iervasi; Letizia Pitto
• Keywords: Male; 0301 basic medicine; mitochondrial impairment; Thyroid Hormones; Myocardial Reperfusion Injury; T3; Mitochondria, Heart; Rats; MicroRNAs; 03 medical and health sciences; Animals, Newborn; cardioprotection; Animals; Triiodothyronine; Myocytes, Cardiac; miRNA; p53; ischemia/reperfusion model; Rats, Wistar; Tumor Suppressor Protein p53; Cells, Cultured; Signal Transduction

Abstract Mitochondrial dysfunctions critically affect cardiomyocyte survival during ischemia/reperfusion (I/R) injury. In this scenario p53 activates multiple signaling pathways that impair cardiac mitochondria and promote cell death. is a validated target of miR-30 whose levels fall under ischemic conditions. Although triiodothyronine (T3) rescues post-ischemic mitochondrial activity viability, no data are available on its role in the modulation I/R. Here we test hypothesis early T3 supplementation rats inhibits post I/R activation pro-death cascade through maintenance miRNA 30a expression. our model, infusion improves recovery performance. At molecular level, beneficial effect associated with restored miR-30a expression area at risk (AAR) correspond to mRNA downregulation. The concomitant decrease protein content reduces Bax limits membrane depolarization resulting preserved function decreased apoptosis necrosis extent AAR. Also primary culture neonatal rats, prevents both downregulation raise induced by hypoxia. regulatory greatly suppressed knockdown. Overall these suggest new mechanism T3-mediated cardioprotection targeted acts, least part, regulation miR-30a/p53 axis.