S100a8/a9 信号导致线粒体功能障碍和心肌细胞死亡
Yulin Li1, Boya Chen1, Xinying Yang1
1Beijing Anzhen Hospital of Capital Medical University and Beijing Institute of Heart Lung and Blood Vessel Diseases, China (Y. Li, B.C., Z.Y., C.Z., Y.J., P.L., Y. Liu, Z.L., B.Q., J.D.).
Circulation
|June 22, 2019
概括
心肌缺血-再输血 (MI/ R) 损伤是一个危急的情况. 这项研究确定S100a8/a9是MI/R损伤的关键媒介,为心脏病发作恢复提供了潜在的治疗点.
科学领域:
- 心血管研究
- 分子医学
- 蛋白质组学和基因组学
背景情况:
- 心肌缺血-再输血 (MI/ R) 损伤是一个重要的临床挑战,治疗选择有限.
- 在识别MI/R损伤的新媒介方面,无偏见的OMIC方法至关重要.
研究的目的:
- 通过动态转录组分析识别MI/R损伤的早期媒介.
- 阐明S100a8/a9在MI/R损伤中的作用和机制.
- 在急性心肌梗塞患者中研究S100a8/ a9的临床相关性.
主要方法:
- 对接受MI/R的小鼠心脏进行动态转录组分析.
- 对S100a8/a9的功能丧失和功能增加研究.
- 在PCI后测量血清S100a8/ a9水平,并对主要心血管不良事件进行随访.
主要成果:
- 在早期再注射过程中,S100a8/ a9被确定为最上调的基因.
- S100a9敲击改善了心脏功能,而过度表达则恶化了损伤.
- 通过TLR4/ERK/PPARGC1A/NRF1信号传递抑制复合物I,诱导了S100a8/a9的线粒体功能障碍.
- S100a9 中和抗体治疗减少了MI/ R损伤.
- 在心脏病发作后血清S100a8/ a9水平升高与心血管不良事件相关.
结论:
- 通过抑制线粒体功能,S100a8/ a9是早期心肌细胞死亡的关键调节剂.
- 针对S100a8/a9介导的信号提供了一个有前途的新疗法来治疗MI/R损伤.
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