Dapagliflozin attenuates LPS-induced myocardial injury by reducing ferroptosis.

IF 2.9 4区 生物学 Q2 BIOPHYSICS
Ke Hu, Pin Jiang, Jiaxin Hu, Bing Song, Ya Hou, Jinxuan Zhao, Haiting Chen, Jun Xie
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引用次数: 0

Abstract

Septic cardiomyopathy is a severe cardiovascular disease with a poor prognosis. Previous studies have reported the involvement of ferroptosis in the pathogenesis of septic cardiomyopathy. SGLT2 inhibitors such as dapagliflozin have been demonstrated to improve ischemia-reperfusion injury by alleviating ferroptosis in cardiomyocyte. However, the role of dapagliflozin in sepsis remains unclear. Therefore, our study aims to investigate the therapeutic effects of dapagliflozin on LPS-induced septic cardiomyopathy. Our results indicate that dapagliflozin improved cardiac function in septic cardiomyopathy experimental mice. Mechanistically, dapagliflozin works by inhibiting the translation of key proteins involved in ferroptosis, such as GPX4, FTH1, and SLC7A11. It also reduces the transcription of lipid peroxidation-related mRNAs, including PTGS2 and ACSL4, as well as iron metabolism genes TFRC and HMOX1.

Abstract Image

达帕格列净通过减少铁蛋白沉积减轻 LPS 诱导的心肌损伤
化脓性心肌病是一种预后不良的严重心血管疾病。以往的研究报告显示,铁蛋白沉积参与了脓毒性心肌病的发病机制。达帕格列净(dapagliflozin)等 SGLT2 抑制剂已被证实可通过减轻心肌细胞的铁蛋白沉积来改善缺血再灌注损伤。然而,达帕格列净在败血症中的作用仍不清楚。因此,我们的研究旨在探讨达帕格列净对 LPS 诱导的脓毒症心肌病的治疗作用。我们的研究结果表明,达帕格列净可改善脓毒症心肌病实验小鼠的心脏功能。从机理上讲,达帕格列净是通过抑制参与铁变态反应的关键蛋白(如 GPX4、FTH1 和 SLC7A11)的翻译来发挥作用的。它还能减少脂质过氧化相关 mRNA 的转录,包括 PTGS2 和 ACSL4,以及铁代谢基因 TFRC 和 HMOX1。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
6.00
自引率
0.00%
发文量
22
审稿时长
6-12 weeks
期刊介绍: The Journal of Bioenergetics and Biomembranes is an international journal devoted to the publication of original research that contributes to fundamental knowledge in the areas of bioenergetics, biomembranes, and transport, including oxidative phosphorylation, photosynthesis, muscle contraction, as well as cellular and systemic metabolism. The timely research in this international journal benefits biophysicists, membrane biologists, cell biologists, biochemists, molecular biologists, physiologists, endocrinologists, and bio-organic chemists.
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