Abstract

Glucagon-like peptide-1 (GLP-1), a novel type of glucose-lowering agent, has been reported to exert cardioprotective effects. However, the cardioprotective mechanism of GLP-1 on spontaneous hypertension-induced cardiac hypertrophy has not been fully elucidated. In this study, we revealed that liraglutide or alogliptin treatment ameliorated spontaneous hypertension-induced cardiac hypertrophy, as evidenced by decreased levels of cardiac hypertrophic markers (atrial natriuretic peptide, brain natriuretic peptide, and β-myosin heavy chain), as well as systolic blood pressure, diastolic blood pressure, mean arterial pressure, and histological changes. Both drugs significantly reduced the levels of angiotensin II (AngII) and AngII type 1 receptor (AT1R) and upregulated the levels of AngII type 2 receptor (AT2R) and angiotensin-converting enzyme 2 (ACE2), as indicated by a reduced AT1R/AT2R ratio. Simultaneously, treatment with liraglutide or alogliptin significantly increased GLP-1 receptor expression and adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and downregulated the phosphorylation of mammalian target of rapamycin (mTOR), p70 ribosomal S6 protein kinase, and eukaryotic translation initiation factor 4E binding protein 1 in spontaneous hypertension rats. Furthermore, our data demonstrated that the AMPK inhibitor compound C or mTOR activator MHY1485 inhibited the anti-hypertrophic effect of GLP-1. In summary, our study suggests that liraglutide or alogliptin protects the heart against cardiac hypertrophy by regulating the expression of AngII/AT1R/ACE2 and activating the AMPK/mTOR pathway, and GLP-1 agonist can be used in the treatment of patients with cardiac hypertrophy.

中文翻译：

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胰高血糖素样肽-1 通过 AngII/AT1R/ACE2 和 AMPK/mTOR/p70S6K 通路减轻心脏肥大

摘要

据报道，胰高血糖素样肽-1 (GLP-1) 是一种新型降糖剂，具有心脏保护作用。然而，GLP-1 对自发性高血压引起的心脏肥大的心脏保护机制尚未完全阐明。在这项研究中，我们发现利拉鲁肽或阿格列汀治疗可改善自发性高血压引起的心脏肥大，这可以通过心脏肥大标志物（心房利钠肽、脑利钠肽和 β-肌球蛋白重链）以及收缩期血液水平的降低来证明血压、舒张压、平均动脉压和组织学变化。两种药物均显着降低血管紧张素 II (AngII) 和 AngII 1 型受体 (AT1R) 的水平，并上调 AngII 2 型受体 (AT2R) 和血管紧张素转换酶 2 (ACE2) 的水平，如 AT1R/AT2R 降低所示比率。同时，利拉鲁肽或阿格列汀治疗显着增加 GLP-1 受体表达和腺苷一磷酸活化蛋白激酶 (AMPK) 磷酸化，并下调哺乳动物雷帕霉素靶蛋白 (mTOR)、p70 核糖体 S6 蛋白激酶和真核翻译起始因子 4E 的磷酸化自发性高血压大鼠中的结合蛋白 1。此外，我们的数据表明，AMPK 抑制剂化合物 C 或 mTOR 激活剂 MHY1485 抑制了 GLP-1 的抗肥大作用。总之，