Modification of cardiac thyroid hormone deiodinases expression in an ischemia/reperfusion rat model after T3 infusion
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Modification of cardiac thyroid hormone deiodinases expression in an ischemia/reperfusion rat model after T3 infusion Laura Sabatino1 · Claudia Kusmic1 · Giorgio Iervasi1 Received: 7 April 2020 / Accepted: 1 August 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
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 Ischemia/reperfusion · Low T3 syndrome · Deiodinases · Gene expression
Introduction Thyroid hormones (TH) have important effects on the heart and the cardiovascular system and act as crucial regulators of blood pressure and vascular resistance [1]. Severe diseases characteristically induce a downregulation of TH metabolism [2]. Patients with either chronic or acute heart failure, even in the absence of TSH alterations, often show low serum T3 levels and this condition has been associated with increased mortality [3, 4]. This status is defined as “low T3 syndrome (LT3)” and has been described in patients with acute events, despite the absent history of thyroidal disease [5]. TH deiodinases are the enzymes mediating the activation and deactivation of thyroid hormones in different tissues. The three known iodothyronine deiodinases are named type 1, 2 and 3 (DIO1, DIO2 and DIO3) and have different * Laura Sabatino [email protected] 1
Institute of Clinical Physiology, National Research Council (C.N.R.), Pisa, Italy
catalytic activities and tissue distribution [6, 7]. DIO1 and DIO2 activate TH and catalyze the 5′-monodeiodination in the outer phenolic ring of the pre
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