Department of Vascular Surgery, Xiamen Cardiovascular Hospital, Xiamen University, Xiamen, Fujian, China.
Department of Vascular Surgery, Xiamen Cardiovascular Hospital, Xiamen University, Xiamen, Fujian, China.
Gene. 2024 Apr 5;901:148171. doi: 10.1016/j.gene.2024.148171. Epub 2024 Jan 18.
At present, meteorin-like protein (METRNL) has been proven to be widely expressed in the myocardium and participates in the pathogenic process of various cardiovascular diseases. However, the effects of METRNL on pathological cardiac hypertrophy is still unknown. In the present study, we used a mouse model of transverse aortic constriction (TAC) surgery to mimic pathological cardiac hypertrophy and gene delivery system to overexpress METRNL in vivo. The results showed that METRNL overexpression improved TAC-induced pathological cardiac hypertrophy in mice and neonatal cardiomyocytes. In addition, METRNL overexpression diminished TAC-induced cardiac oxidative damage, inflammation and cardiomyocyte apoptosis. Moreover, the cardioprotective effect of METRNL overexpression was directly related to the activation of AMP-activated protein kinase (AMPK) and sirtuin1 (SIRT1). In summary, our data identified that METRNL may be a promising therapeutic target to mitigate pathological cardiac hypertrophy in the future.
目前,已证实 meteorin-like protein(METRNL)在心肌中广泛表达,并参与各种心血管疾病的发病过程。然而,METRNL 对病理性心肌肥厚的影响尚不清楚。在本研究中,我们使用了横主动脉缩窄(TAC)手术的小鼠模型来模拟病理性心肌肥厚,并采用基因传递系统在体内过表达 METRNL。结果表明,METRNL 的过表达改善了 TAC 诱导的小鼠和新生心肌细胞的病理性心肌肥厚。此外,METRNL 的过表达减轻了 TAC 诱导的心脏氧化损伤、炎症和心肌细胞凋亡。此外,METRNL 过表达的心脏保护作用与 AMP 激活的蛋白激酶(AMPK)和沉默调节蛋白 1(SIRT1)的激活直接相关。总之,我们的数据表明,METRNL 可能是未来减轻病理性心肌肥厚的有前途的治疗靶点。