Modification of cardiac thyroid hormone deiodinases expression in an ischemia/reperfusion rat model after T3 infusion

Mol Cell Biochem. 2020 Dec;475(1-2):205-214. doi: 10.1007/s11010-020-03873-w. Epub 2020 Aug 11.

Abstract

The deiodinases regulate the activation and inactivation of Thyroid hormones (TH), in both physiological and pathological conditions. The three deiodinases, DIO1, DIO2 and DIO3, have different catalytic role and cellular and tissue distribution. Aim of this study is to evaluate a rat model of regional ischemia/reperfusion (I/R), the modification of cardiac main function after the administration of 6 µg/kg/day of triiodothyronine (T3), and the associated to DIO1, DIO2 and DIO3 gene expression. We also aim to study DIO1 and DIO2 protein levels in different left ventricular regions after an ischemic event. Four groups of rats were studied: sham-operated, sham-operated + T3, I/R rats and I/R rats + T3. DIO1, DIO2 and DIO3 expression were evaluated in I/R region (AAR: area-at-risk) and in a more distant region from ischemic wound (RZ: remote zone). In I/R group, circulating free-T3 (FT3) levels were significantly decreased with respect to basal values, whereas in I/R + T3 rats, FT3 levels were comparable to basal values. In AAR of I/R + T3 rats, DIO1 and DIO2 gene expression significantly increased with respect to sham. In RZ, DIO1 and DIO3 gene expression was significantly lower in sham and I/R rats when compared to I/R + T3. In sham + T3 group, DIO1 and DIO2 gene expression was not detectable, whereas DIO3 was significantly higher than in the other three groups. The present study gives interesting new insights on DIO1, DIO2 and DIO3 in the ischemic heart and their role in relation to T3-mediated amelioration of cardiac function and structure.

Keywords: Deiodinases; Gene expression; Ischemia/reperfusion; Low T3 syndrome.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Heart / drug effects
  • Heart / physiology*
  • Infusions, Intravenous
  • Iodide Peroxidase / genetics
  • Iodide Peroxidase / metabolism*
  • Male
  • Rats
  • Rats, Wistar
  • Reperfusion Injury / drug therapy
  • Reperfusion Injury / metabolism*
  • Reperfusion Injury / pathology
  • Thyroid Hormones / metabolism*
  • Triiodothyronine / administration & dosage*

Substances

  • Thyroid Hormones
  • Triiodothyronine
  • Iodide Peroxidase