Liang Sumei, Han Juanping, Cheng Weiping, Chen Xiaoan
Department of Cardiology, Xi'an International Medical Center Hospital, Xi'an, Shaanxi 730050, China.
Department of Cardiac Surgery, Xi'an International Medical Center Hospital, Xi'an, Shaanxi 730050, China.
Int Immunopharmacol. 2023 Feb;115:109678. doi: 10.1016/j.intimp.2023.109678. Epub 2023 Jan 10.
C1q/tumor necrosis factor-related protein-6 (CTRP6) is a multifunctional protein that plays a pivotal role in diverse physiological and pathological processes. To date, whether CTRP6 has a role in myocardial ischemia-reperfusion (I/R) injury remains unexplored. This work aimed to investigate the potential role and mechanism of CTRP6 in myocardial I/R injury through in vitro and in vivo experiments. CTRP6 expression was downregulated in hypoxia/reoxygenation (H/R)-treated cardiomyocytes. The apoptosis, oxidative stress, and inflammation in the H/R-treated cardiomyocytes were markedly alleviated by CTRP6 overexpression or exacerbated by CTRP6 silencing. Notably, the overexpression of CTRP6 remarkably ameliorated the myocardial injury, infarction area, cardiac apoptosis, oxidative stress, and inflammation in mice with myocardial I/R injury in vivo. Further investigation revealed that CTRP6 overexpression enhanced the activation of Nrf2 in the H/R-treated cardiomyocytes and the myocardium tissue of mice with myocardial I/R injury. CTRP6 overexpression increased the phosphorylated level of Akt and GSK-3β, and the inhibition of Akt abolished CTRP6-overexpression-elicited Nrf2 activation in the H/R-treated cardiomyocytes. Additionally, the inhibition of Akt or Nrf2 abolished the protective effects of CTRP6 overexpression on the H/R-treated cardiomyocytes. Altogether, CTRP6 had protective effects on myocardial I/R injury via the effects on the Akt-GSK-3β-Nrf2 signaling cascade. Our work recommends CTRP6 as a novel cardioprotective target for the treatment of myocardial I/R injury.
C1q/肿瘤坏死因子相关蛋白6（CTRP6）是一种多功能蛋白，在多种生理和病理过程中发挥关键作用。迄今为止，CTRP6在心肌缺血再灌注（I/R）损伤中是否发挥作用仍未得到探索。这项工作旨在通过体外和体内实验研究CTRP6在心肌I/R损伤中的潜在作用和机制。在缺氧/复氧（H/R）处理的心肌细胞中，CTRP6表达下调。CTRP6过表达显著减轻了H/R处理的心肌细胞中的凋亡、氧化应激和炎症，而CTRP6沉默则使其加剧。值得注意的是，CTRP6过表达显著改善了体内心肌I/R损伤小鼠的心肌损伤、梗死面积、心脏凋亡、氧化应激和炎症。进一步研究发现，CTRP6过表达增强了H/R处理的心肌细胞和心肌I/R损伤小鼠心肌组织中Nrf2的激活。CTRP6过表达增加了Akt和GSK-3β的磷酸化水平，抑制Akt可消除CTRP6过表达诱导的H/R处理心肌细胞中Nrf2的激活。此外，抑制Akt或Nrf2可消除CTRP6过表达对H/R处理心肌细胞的保护作用。总之，CTRP6通过影响Akt-GSK-3β-Nrf2信号级联对心肌I/R损伤具有保护作用。我们的研究推荐CTRP6作为治疗心肌I/R损伤的新型心脏保护靶点。
