Mild Therapeutic Hypothermia Alleviated Myocardial Ischemia/Reperfusion Injury via Targeting SLC25A10 to Suppress Mitochondrial Apoptosis

IF 2.4 3区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS
Senlin Ma, Yun Song, Yanxin Xu, Chao Wang, Yifan Yang, Yanchao Zheng, Qiuxin Lu, Qingjiang Chen, Jian Wu, Bin Wang, Mingquan Chen
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Abstract

Myocardial ischemia/reperfusion injury (MI/RI) is identified as a severe vascular emergency, and the treatment strategy of MI/RI still needs further improvement. The present study aimed to investigate the potential effects of mild therapeutic hypothermia (MTH) on MI/RI and underlying mechanisms. In ischemia/reperfusion (I/R) rats, MTH treatment significantly improved myocardial injury, attenuated myocardial infarction, and inhibited the mitochondrial apoptosis pathway. The results of proteomics identified SLC25A10 as the main target of MTH treatment. Consistently, SLC25A10 expressions in I/R rat myocardium and hypoxia and reoxygenation (H/R) cardiomyocytes were significantly suppressed, which was effectively reversed by MTH treatment. In H/R cardiomyocytes, MTH treatment significantly improved cell injury, mitochondrial dysfunction, and inhibited the mitochondrial apoptosis pathway, which were partially reversed by SLC25A10 deletion. These findings suggested that MTH treatment could protect against MI/RI by modulating SLC25A10 expression to suppress mitochondrial apoptosis pathway, providing new theoretical basis for clinical application of MTH treatment for MI/RI.

Graphical Abstract

轻度治疗性低温通过靶向 SLC25A10 抑制线粒体凋亡减轻心肌缺血再灌注损伤
心肌缺血再灌注损伤(MI/RI)被认为是一种严重的血管急症,其治疗策略仍需进一步改进。本研究旨在探讨轻度治疗性低温(MTH)对心肌缺血再灌注损伤的潜在影响及其机制。在缺血再灌注(I/R)大鼠中,MTH治疗能明显改善心肌损伤,减轻心肌梗死,抑制线粒体凋亡通路。蛋白质组学研究结果表明,SLC25A10是MTH治疗的主要靶点。一致的是,SLC25A10在I/R大鼠心肌和缺氧再氧(H/R)心肌细胞中的表达被显著抑制,而MTH治疗能有效逆转这一现象。在H/R心肌细胞中,MTH治疗可明显改善细胞损伤、线粒体功能障碍和抑制线粒体凋亡途径,而SLC25A10缺失可部分逆转这些损伤和抑制。这些研究结果表明,MTH治疗可通过调节SLC25A10的表达来抑制线粒体凋亡途径,从而保护心肌缺血/心肌梗死,为MTH治疗心肌缺血/心肌梗死的临床应用提供了新的理论依据。
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来源期刊
Journal of Cardiovascular Translational Research
Journal of Cardiovascular Translational Research CARDIAC & CARDIOVASCULAR SYSTEMS-MEDICINE, RESEARCH & EXPERIMENTAL
CiteScore
6.10
自引率
2.90%
发文量
148
审稿时长
6-12 weeks
期刊介绍: Journal of Cardiovascular Translational Research (JCTR) is a premier journal in cardiovascular translational research. JCTR is the journal of choice for authors seeking the broadest audience for emerging technologies, therapies and diagnostics, pre-clinical research, and first-in-man clinical trials. JCTR''s intent is to provide a forum for critical evaluation of the novel cardiovascular science, to showcase important and clinically relevant aspects of the new research, as well as to discuss the impediments that may need to be overcome during the translation to patient care.
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