Department of Cardiology, Gaochun People's Hospital, Nanjing, China.
Department of Emergency, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Peptides. 2022 Nov;157:170878. doi: 10.1016/j.peptides.2022.170878. Epub 2022 Sep 13.
G protein-coupled receptors (GPCRs) are the largest family of membrane receptors that mediate the effects of cardiac diseases. GPR30, also named G-protein-coupled estrogen receptor, shows beneficial effect on female patients with heart failure. This research aimed to probe the role and mechanism of GPR30 in myocardial hypertrophy. The model of cardiac hypertrophy was induced by infusion of angiotensin (Ang) II in mice, and was induced by Ang II treatment in neonatal rat cardiomyocyte (NRCM). The mouse model of myocardial hypertrophy was induced by angiotensin (Ang) Ⅱ, and the neonatal rat cardiomyocyte (NRCM) was induced by Ang Ⅱ treatment. GPR30 agonist G1 reduced cardiac hypertrophy induced by Ang II in mice, and reduced cardiac atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and β-myosin heavy chain (β-MHC) induced by Ang II. Ang Ⅱ treatment of myocardial fibrosis in mice was suppressed after administration of G1. GPR30 deficiency produced the opposite results. Oxidative stress and apoptosis were enhanced in the mice heart induced by Ang II, which were suppressed by G1 administration, but were further exacerbated after GPR30 deficiency. The outcomes demonstrated that GPR30 participated in the regulation of cardiac hypertrophy and fibrosis. Activation of GPR30 ameliorated cardiac hypertrophy and fibrosis by reducing oxidative stress and apoptosis.
G 蛋白偶联受体（GPCRs）是介导心脏疾病效应的最大的一类膜受体，GPR30 也被称为 G 蛋白偶联雌激素受体，对心力衰竭的女性患者有有益作用。本研究旨在探讨 GPR30 在心肌肥厚中的作用和机制。心肌肥厚模型通过在小鼠中输注血管紧张素（Ang）II 诱导，通过 Ang II 处理新生大鼠心肌细胞（NRCM）诱导。心肌肥厚的小鼠模型是通过血管紧张素（Ang）Ⅱ诱导的，新生大鼠心肌细胞（NRCM）是通过 Ang Ⅱ处理诱导的。GPR30 激动剂 G1 可减少 Ang II 诱导的小鼠心肌肥厚，并减少 Ang II 诱导的心肌心房利钠肽（ANP）、脑利钠肽（BNP）和β-肌球蛋白重链（β-MHC）。G1 给药后可抑制 Ang II 处理的小鼠心肌纤维化。GPR30 缺失则产生相反的结果。Ang II 诱导的小鼠心脏氧化应激和细胞凋亡增强，G1 给药可抑制其作用，但 GPR30 缺失后进一步加重。这些结果表明，GPR30 参与了心脏肥大和纤维化的调节。激活 GPR30 可通过减少氧化应激和细胞凋亡来改善心肌肥厚和纤维化。
