Laboratory of Cell Biology and Functional Anatomy, Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 2415, São Paulo, SP, 05508-900, Brazil.
Basic Res Cardiol. 2015 Sep;110(5):49. doi: 10.1007/s00395-015-0504-7. Epub 2015 Jul 23.
Elevated thyroid hormone (TH) levels induce cardiac hypertrophy partially via type 1 Angiotensin II receptor (AT1R). MicroRNAs (miRNAs) are key regulators of cardiac homeostasis, and miR-133 has been shown to be involved in cardiac hypertrophy. However, the potential role of miR-133 in cardiac growth induced by TH is unknown. Thus, we aimed to investigate the miR-133 expression, as well as its potential role in cardiac hypertrophy in response to TH. Wistar rats were subjected to hyperthyroidism combined or not with the AT1R blocker. T3 serum levels were assessed to confirm the hyperthyroid status. TH induced cardiac hypertrophy, as evidenced by higher cardiac weight/tibia length ratio and α-actin mRNA levels, which was prevented by AT1R blocker. miR-133 expression was decreased in TH-induced cardiac hypertrophy in part through the AT1R. Additionally, the cardiac mRNA levels of miR-133 targets, SERCA2a and calcineurin were increased in hyperthyroidism partially via AT1R, as evaluated by real-time RT-PCR. Interestingly, miR-133 levels were unchanged in T3-induced cardiomyocyte hypertrophy in vitro. However, a gain-of-function study revealed that miR-133 mimic blunted the T3-induced cardiomyocyte hypertrophy in vitro. Together, our data indicate that miR-133 expression is reduced in TH-induced cardiac hypertrophy partially by the AT1R and that miR-133 mimic prevents the cardiomyocyte hypertrophy in response to T3 in vitro. These findings provide new insights regarding the mechanisms involved in the cardiac growth mediated by TH, suggesting that miR-133 plays a key role in TH-induced cardiomyocyte hypertrophy.
甲状腺激素（TH）水平升高部分通过 1 型血管紧张素 II 受体（AT1R）诱导心肌肥厚。microRNAs（miRNAs）是心脏内稳态的关键调节因子，已经证明 miR-133 参与了心肌肥厚。然而，TH 诱导的心脏生长中 miR-133 的潜在作用尚不清楚。因此，我们旨在研究 miR-133 的表达及其在 TH 诱导的心肌肥厚中的潜在作用。Wistar 大鼠接受甲状腺功能亢进症治疗，同时或不接受 AT1R 阻滞剂治疗。通过检测 T3 血清水平来确认甲状腺功能亢进症的状态。TH 诱导的心肌肥厚，表现为心脏重量/胫骨长度比和α-肌动蛋白 mRNA 水平升高，这一现象被 AT1R 阻滞剂所阻止。miR-133 的表达在 TH 诱导的心肌肥厚中部分通过 AT1R 减少。此外，通过实时 RT-PCR 评估，我们发现，在甲状腺功能亢进症中，miR-133 靶标 SERCA2a 和钙调神经磷酸酶的心脏 mRNA 水平增加，这部分是通过 AT1R 实现的。有趣的是，miR-133 水平在体外 T3 诱导的心肌细胞肥厚中没有变化。然而，功能获得研究表明，miR-133 模拟物在体外减轻了 T3 诱导的心肌细胞肥厚。综上所述，我们的数据表明，miR-133 的表达在 TH 诱导的心肌肥厚中部分通过 AT1R 减少，miR-133 模拟物可防止体外 T3 诱导的心肌细胞肥厚。这些发现为 TH 介导的心脏生长机制提供了新的见解，表明 miR-133 在 TH 诱导的心肌细胞肥厚中发挥关键作用。
