Xu Xiaohua, Wan Wenhan, Garza Michael A, Zhang John Q
Laboratory of Cardiovascular Research, The University of Texas at San Antonio, UTSA Circle 1, San Antonio, TX, 78249, USA.
J Physiol Sci. 2018 Nov;68(6):743-748. doi: 10.1007/s12576-017-0587-z. Epub 2017 Dec 22.
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.
甲状腺激素受体(TRs)在心肌收缩力主要决定因素相关基因的表达中起关键作用,这些基因包括α-肌球蛋白重链(α-MHC)和β-肌球蛋白重链(β-MHC)。心肌梗死(MI)后,心肌TRs的变化与甲状腺激素(TH)靶基因转录的变化始终相关,这被认为在终末期心力衰竭的进展中起关键作用。有趣的是,MI后运动训练已被证明可有益地改变TH靶基因转录并保留心脏功能,而不改变血清TH水平。因此,在本研究中,我们调查了轻度运动训练是否会改变MI后大鼠中α1和β1 TR亚型的表达。7周龄雄性Sprague-Dawley大鼠接受冠状动脉结扎或假手术,并分为3组(n = 10):假手术组、久坐不动的MI组(MI-Sed)和运动的MI组(MI-Ex)。MI后1周开始跑步机训练,并逐渐增加至16米/分钟、5°坡度、每天50分钟、每周5天,共持续8周。进行实时聚合酶链反应和凝胶电泳以量化TR亚型的变化。我们的结果表明,两种MI组中TR-α1和TR-β1的mRNA表达均较高;然而,蛋白质电泳数据显示,MI-Ex组中的TR-α1比MI-Sed组高1.91倍(P < 0.05),TR-β1比MI-Sed组高1.62倍(P < 0.05)。MI后,存活的非梗死心肌中TR-α1和TR-β1蛋白水平显著降低。中等强度运动训练显著增加TR-α1和TR-β1蛋白表达,这反过来可能上调α-MHC并改善心肌收缩功能和预后。