Overexpression of myofibrillogenesis regulator-1 aggravates cardiac hypertrophy induced by angiotensin II in mice
Overexpression of myofibrillogenesis regulator-1 aggravates cardiac hypertrophy induced by angiotensin II in mice
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DOI：
10.1161/hypertensionaha.106.085399
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发表时间：
2007-06-01
期刊：
影响因子：
8.3
通讯作者：
Liu, De-Pei
中科院分区：
文献类型：
--
作者：
Li, Hong-Liang;She, Zhi-Gang;Liu, De-Pei
肌原纤维生成调节因子-1（MR-1）增强血管紧张素II（Ang II）诱导的心肌细胞肥大。然而，其在体内心脏肥大中的作用仍不清楚。本研究旨在探讨MR-1是否能促进血管紧张素II诱导的心肌肥厚，并阐明MR-1对心肌肥厚的分子机制。我们使用了一个模型，血管紧张素II诱导的心脏肥大的血管紧张素II输注雌性小鼠。在接受Ang II输注的野生型小鼠中，2周后出现心脏肥大。然而，在过表达人MR-1（转基因）的小鼠中，心脏肥大显著大于野生型小鼠，如通过心脏重量：体重比、心肌细胞面积和超声心动图测量以及心脏心房利钠肽和B型利钠肽mRNA和蛋白水平估计的。我们进一步的研究结果表明，在野生型Ang II小鼠中观察到的心脏炎症和纤维化在转基因Ang II小鼠中增强。重要的是，增加核因子κ B激活显着增加转基因小鼠与野生型小鼠相比，血管紧张素II输注2周后。体外实验还显示，MR-1的过表达增强了Ang II诱导的核因子κ B激活，而MR-1的下调则阻断了心肌细胞中的核因子κ B激活。总之，我们的研究结果表明，MR-1通过激活核因子κ B信号通路在心肌肥厚的发展中发挥了抑制作用。
Myofibrillogenesis regulator-1 (MR-1) augments cardiomyocytes hypertrophy induced by angiotensin II (Ang II) in vitro. However, its roles in cardiac hypertrophy in vivo remain unknown. Here, we investigate whether MR-1 can promote cardiac hypertrophy induced by Ang II in vivo and elucidate the molecular mechanisms of MR-1 on cardiac hypertrophy. We used a model of Ang II-induced cardiac hypertrophy by infusion of Ang II in female mice. In wild-type mice subjected to the Ang II infusion, cardiac hypertrophy developed after 2 weeks. In mice overexpressing human MR-1 (transgenic), however, cardiac hypertrophy was significantly greater than in wild-type mice as estimated by heart weight: body weight ratio, cardiomyocyte area, and echocardiographic measurements, as well as cardiac atrial natriuretic peptide and B-type natriuretic peptide mRNA and protein levels. Our further results showed that cardiac inflammation and fibrosis observed in wild-type Ang II mice were augmented in transgenic Ang II mice. Importantly, increased nuclear factor kappa B activation was significantly increased higher in transgenic mice compared with wild-type mice after 2 weeks of Ang II infusion. In vitro experiments also revealed that overexpression of MR-1 enhanced Ang II-induced nuclear factor kappa B activation, whereas downregulation of MR-1 blocked it in cardiac myocytes. In conclusion, our results suggest that MR-1 plays an aggravative role in the development of cardiac hypertrophy via activation of the nuclear factor kappa B signaling pathway.