SUCNR 1通过诱导内细胞网膜应激介导的ER-mito交叉通话来促进动脉样硬化
Chuchu Yuan1, Bo Yu1, Lu Li2
1Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.
International immunopharmacology
|November 1, 2024
概括
酸盐受体1 (SUCNR1) 通过增加内质网膜应激和线粒体损伤来促进动脉样硬化. 抑制这种途径可能为心血管疾病提供新的治疗策略.
科学领域:
- 心血管生物学 心血管生物学
- 分子医学是分子医学.
- 炎症研究 炎症研究
背景情况:
- 动脉样硬化是一种慢性炎症性动脉疾病.
- 酸盐受体1 (SUCNR1) 在动脉样硬化病原体中的作用尚未完全理解.
- SUCNR1参与调节心血管疾病中的炎症反应.
研究的目的:
- 研究SUCNR1在动脉样硬化的发展和进展中的作用.
- 阐明SUCNR1影响动脉样硬化病变的分子机制.
- 探索与动脉样硬化中SUCNR1信号传递相关的潜在治疗点.
主要方法:
- 在人类动脉样硬化病变中分析SUCNR1表达.
- 使用高脂肪饮食中的ApoE-/-小鼠内皮细胞中的SUCNR1淘汰模型.
- 研究SUCNR1过度表达/激活对内分泌网膜 (ER) 应激,线粒体功能和cGAS-STING通路激活的影响.
- 评估ER压力抑制剂对SUCNR1诱导病理学的影响.
主要成果:
- 在人类动脉样硬化病变的内皮细胞中,SUCNR1的表达升高.
- 在血管内皮细胞中删除SUCNR1,在小鼠中减弱了动脉样硬化病变的进展.
- SUCNR1激活加剧了ER压力,ER-线粒体交叉声,线粒体损伤和mtDNA泄漏.
- SUCNR1促进了cGAS-STING信号通路的激活.
- 抑制ER压力逆转了SUCNR1诱导的线粒体损伤,ER-线粒体相互作用和炎症.
结论:
- SUCNR1通过通过ER压力信号和激活下游cGAS-STING通路来调解ER-线粒体交叉,促进动脉样硬化.
- 针对ER压力信号,为动脉样硬化提供了一个潜在的治疗策略.
- SUCNR1被确定为动脉样硬化背后的炎症机制的关键参与者.
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