Post-myocardial infarction exercise training beneficially regulates thyroid hormone receptor isoforms

Abstract

Thyroid hormone receptors (TRs) play a critical role in the expression of genes that are major determinants of myocardial contractility, including α-myosin heavy chain (α-MHC) and β-MHC. After myocardial infarction (MI), changes in myocardial TRs consistently correlate with changes in thyroid hormone (TH) target gene transcription, and this is thought to play a key role in the progression to end-stage heart failure. Interestingly, post-MI exercise training has been shown to beneficially alter TH-target gene transcription and preserve cardiac function without changing serum TH. Therefore, in this study, we investigated whether mild exercise training alters expression of α1 and β1 TR isoforms in post-MI rats. Seven-week-old male Sprague-Dawley rats underwent coronary ligation or sham operation, and were assigned to 3 groups (n = 10): sham, sedentary MI (MI-Sed), and exercise MI (MI-Ex). Treadmill training was initiated 1 week post-MI, and gradually increased up to 16 m/min, 5° incline, 50 min/day, 5 days/week, and lasted for a total of 8 weeks. Real-time polymerase chain reaction and gel electrophoresis were performed to quantify changes in TR isoforms. Our results illustrated that mRNA expression of TR-α1 and TR-β1 was higher in both MIs; however, protein electrophoresis data showed that TR-α1 was 1.91-fold higher (P < 0.05) and TR-β1 was 1.62-fold higher (P < 0.05) in the MI-Ex group than in the MI-Sed group. After MI, TR-α1 and TR-β1 protein levels are significantly decreased in the surviving non-infarcted myocardium. Moderate-intensity exercise training significantly increases TR-α1 and TR-β1 protein expression, which in turn may upregulate α-MHC and improve myocardial contractile function and prognosis.

Keywords: Exercise training; Myocardial infarction; Thyroid hormone receptors.

Fig. 1

Exercise-induced TR isoform gene expressions in post-infarcted rat heart. There were no significant differences in both TR-α1 and TR-β1 between MI-Ex and MI-Sed groups. Data are expressed as ratios of target genes to β-actin relative to Sham. Values are mean ± SE

Fig. 2

Electrophoresis results of TR-α1 and TR-β1 protein expression. Both MI-Ex and Sham animals had significantly higher TR-α1 and TR-β1 protein expression than MI-Sed group. There were no significant differences in TR-α1 and TR-β1 between Sham and MI-Ex rats