Department of Pharmacology, University of Athens, Goudi, Athens, Greece.
Horm Metab Res. 2010 Sep;42(10):718-24. doi: 10.1055/s-0030-1255035. Epub 2010 Jun 17.
Thyroid hormone (TH) signaling is altered in response to various stresses including myocardial ischemia. The present study investigated potential implication of TH signaling in the pathophysiology of postischemic remodeling. Acute myocardial infarction was induced in rats by coronary artery ligation (AMI). After 34 weeks, 6 animals were on congestive heart failure (CHF) as indicated by measurements in lung and right ventricular weight. 7 animals were in compensated state (Non-CHF) and 8 sham-operated animals (SHAM) served as controls. Progression to congestive heart failure was characterized by marked decrease in EF% and all other functional echocardiographic parameters. Furthermore, beta-MHC expression was significantly increased in CHF. A distinct pattern of thyroid hormone receptor (TR) expression was observed in the course of postischemic remodeling; TR alpha 1 was upregulated and TR beta 1 was downregulated in Non-CHF, and TR alpha 1 expression was markedly decreased during the transition from Non-CHF to CHF resulting in tissue hypothyroidism. Circulating T3 and T4 remained unchanged. This response was associated with marked decrease in mTOR activation. A potential link between mTOR and TR alpha 1 expression was shown in a neonatal cardiomyocytes model of PE (phenylephrine)-induced pathological growth. Phenylephrine increased the expression of TR alpha 1 in nucleus and this response was abrogated in the case of mTOR inhibition by rapamycin. In conclusion, progression to congestive heart failure after myocardial infarction is associated with suppressed expression of TR alpha 1 and results in tissue hypothyroidism. This process may, at least in part, be mTOR dependent.
甲状腺激素（TH）信号会因各种应激而改变，包括心肌缺血。本研究探讨了 TH 信号在缺血后重构病理生理学中的潜在意义。通过冠状动脉结扎（AMI）在大鼠中诱导急性心肌梗死。34 周后，6 只动物出现充血性心力衰竭（CHF），表现为肺和右心室重量的测量值。7 只动物处于代偿状态（非 CHF），8 只假手术动物（SHAM）作为对照。进展为充血性心力衰竭的特征是 EF%和所有其他功能超声心动图参数明显下降。此外，β-MHC 表达在 CHF 中显著增加。在缺血后重构过程中观察到甲状腺激素受体（TR）表达的明显模式；在非 CHF 中，TRα1上调，TRβ1下调，而在非 CHF 向 CHF 的转变过程中，TRα1表达明显下降，导致组织甲状腺功能减退。循环 T3 和 T4 保持不变。这种反应与 mTOR 激活的明显减少有关。在去甲肾上腺素（phenylephrine）诱导的病理性生长的新生儿心肌细胞模型中显示了 mTOR 和 TRα1 表达之间的潜在联系。phenylephrine 增加了核内 TRα1 的表达，而在 rapamycin 抑制 mTOR 的情况下，这种反应被阻断。总之，心肌梗死后进展为充血性心力衰竭与 TRα1 表达受抑制有关，并导致组织甲状腺功能减退。这个过程至少部分可能依赖于 mTOR。
