血小板中的内源性SIRT6负面调节血小板激活和血栓形成
Yanli Liu1, Tao Wang1, Qilong Zhou1
1Department of Neurosurgery, Laboratory of Ethnopharmacology, Tissue-orientated Property of Chinese Medicine Key Laboratory of Sichuan Province, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, China.
Frontiers in pharmacology
|January 8, 2024
概括
血小板Sirtuin 6 (SIRT6) 通过抑制血小板激活和血栓形成,在预防心血管疾病方面发挥着至关重要的作用. 血小板中SIRT6的损失加剧了血栓事件,而它的激活提供了保护.
科学领域:
- 心血管生物学 心血管生物学
- 血液学 血液学 血液学
- 分子医学是分子医学.
背景情况:
- 血小板功能障碍对心血管疾病和血栓塞栓症有重大影响.
- 已知Sirtuin 6 (SIRT6) 是一种依赖NAD+的酶,当它不在内皮细胞中时,它会参与动脉血栓形成.
- 血小板内内源性SIRT6对血小板激活和血栓形成的具体作用尚不清楚.
研究的目的:
- 研究血小板内源SIRT6在血小板激活和血栓形成过程中的调节作用.
- 阐明SIRT6影响血小板功能的潜在分子机制.
主要方法:
- 使用SIRT6-Knockout (SIRT6-/-) 和野生类型 (WT) 的小鼠.
- 评估了血小板激活,聚合和凝块收缩.
- 进行了血小板采用转移实验.
- 在FeCl3诱导的动脉血栓形成模型中分析了血栓封闭时间.
- 研究了9型蛋白转化酶 (PCSK9) 和基因激活蛋白激酶 (MAPK) 信号通路的表达和释放.
主要成果:
- 来自SIRT6-/-小鼠的血小板显示出增强的血栓诱导激活,聚合和凝块收缩.
- 通过激素UBCS039激活SIRT6,对血小板激活和动脉血栓形成产生保护作用.
- 血小板中SIRT6的损失在体内显著延长了血栓封闭时间.
- SIRT6缺乏导致血小板PCSK9的表达/释放增加,激活MAPK信号传递.
结论:
- 血小板内源性SIRT6在调节血小板激活和血栓形成方面发挥着新的保护作用.
- SIRT6抑制了血小板PCSK9分泌和MAPK信号传递,从而减轻了血栓事件.
- 这些发现提供了针对血小板SIRT6.6的潜在治疗策略.
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