Selenoproteins regulate contractility during hyperthyroidism‐induced cardiac hypertrophy

Abstract

We assessed the hypothesis that selenoproteins are important for the heart during hyperthyroidism‐induced myocardial hypertrophy. Mice were injected with 1mg/kg triiodothyronine (T3) or vehicle control for 8 days. Expression levels of several selenoproteins were found to increase in heart tissue with T3‐treatment, with some of the most elevated mRNAs including selenoprotein R (Sel R), thioredoxin reductase−1, and both glutathione peroxidase (GPX)−1 and −3. T3‐treatment induced increases in thioredoxin reductase activity as well as GPX−4 and Sel R, but not GPX−1, proteins. We next utilized a mouse model (trspfl/fl X αMHC‐Cre), which involves reduced expression of Sec‐tRNA in the heart. The mice expressing reduced levels of Sec‐tRNA in the heart (Cre+ mice) developed similar levels of myocardial hypertrophy upon T3 injection compared to negative controls (Cre− mice) as determined by heart mass:body mass. As expected, T3‐treatment of Cre− mice resulted in altered cardiac parameters including increased fractional shortening, decreased systolic left ventricular inner diameter, and increased intraventricular septal thickness. In contrast, these cardiac parameters were not altered in Cre+ mice. These results suggest that restricting the elevation of selenoprotein synthesis by reducing Sec‐tRNA levels may lead to a loss of contractility needed for maintaining cardiac function during hypertrophy.