Department of Cardiovascular Medicine, The Second Hospital of Hebei Medical University, Heping West Road No. 215, Shijiazhuang, 050000, China.
Handan Central Hospital, Handan, 056000, China.
Biol Direct. 2024 Aug 2;19(1):62. doi: 10.1186/s13062-024-00505-x.
High glucose levels are key factors and key contributors to several cardiovascular diseases associated with cardiomyocyte injury. Ferroptosis, which was identified in recent years, is a mode of cell death caused by the iron-mediated accumulation of lipid peroxides. Neuregulin-4 (Nrg4) is an adipokine that has protective effects against metabolic disorders and insulin resistance. Our previous study revealed that Nrg4 has a protective effect against diabetic myocardial injury, and the aim of this study was to investigate whether Nrg4 could attenuate the occurrence of high glucose-induced ferroptosis in cardiomyocytes.
We constructed an in vivo diabetic myocardial injury model in which primary cardiomyocytes were cultured in vitro and treated with Nrg4. Changes in ferroptosis-related protein levels and ferroptosis-related indices in cardiomyocytes were observed. In addition, we performed back-validation and explored signalling pathways that regulate ferroptosis in primary cardiomyocytes.
Nrg4 attenuated cardiomyocyte ferroptosis both in vivo and in vitro. Additionally, the AMPK/NRF2 signalling pathway was activated during this process, and when the AMPK/NRF2 pathway was inhibited, the beneficial effects of Nrg4 were attenuated.
Nrg4 antagonizes high glucose-induced ferroptosis in cardiomyocytes via the AMPK/NRF2 signalling pathway.
高糖水平是与心肌细胞损伤相关的几种心血管疾病的关键因素和关键促成因素。铁介导的脂质过氧化物积累引起的细胞死亡模式 Ferroptosis 是近年来才被发现的。Neuregulin-4（Nrg4）是一种脂肪细胞因子，对代谢紊乱和胰岛素抵抗具有保护作用。我们之前的研究表明，Nrg4 对糖尿病性心肌损伤具有保护作用，本研究旨在探讨 Nrg4 是否可以减轻高糖诱导的心肌细胞铁死亡的发生。
我们构建了体内糖尿病心肌损伤模型，体外培养原代心肌细胞并给予 Nrg4 处理。观察心肌细胞中铁死亡相关蛋白水平和铁死亡相关指标的变化。此外，我们进行了验证，并探讨了调节原代心肌细胞铁死亡的信号通路。
Nrg4 减轻了体内和体外心肌细胞的铁死亡。此外，在此过程中激活了 AMPK/NRF2 信号通路，当抑制 AMPK/NRF2 通路时，Nrg4 的有益作用减弱。
Nrg4 通过 AMPK/NRF2 信号通路拮抗高糖诱导的心肌细胞铁死亡。
