ангиотензин II 诱导血管内皮功能障碍通过通过 CD36 促进脂质过氧化介导的铁死
Qian Zhou1, Ying Zhang1, Wei Shi1
1Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China.
Biomolecules
|November 27, 2024
概括
ангиотензин II (Ang II) 在人静脉内皮细胞 (HUVEC) 中诱导铁,导致血管功能障碍. 抑制铁亡,特别是向CD36,可能为高血压相关的血管损伤提供治疗策略.
科学领域:
- 心血管生物学 心血管生物学
- 细胞病理学细胞病理学
- 分子医学是分子医学.
背景情况:
- ангиотензин II (Ang II) 是氨酸 - ангиотензин - 阿尔多素系统 (RAAS) 中的关键血管收缩剂,与内皮功能障碍有关.
- 铁亡是一种受调节的细胞死亡形式,因其在心血管疾病中的作用越来越受认可.
研究的目的:
- 研究人类静脉内皮细胞 (HUVECs) 中Ang II诱导的铁亡的作用和机制.
- 确定潜在的分子标,以减轻高血压中的血管内皮损伤和功能障碍.
主要方法:
- HUVEC暴露于不同度的Ang II.
- 评估了氧化应激,亡,氧化 (NO) 释放,内甲素-1 (ET-1) 含量和蛋白质表达 (ZO-1,p-eNOS,VE-cadherin,Occludin,ICAM-1) 的标志物.
- 分析了脂质代谢,与铁亡相关的分子 (Fe2+,MDA,GSH,GPX4,SLC7A11,SLC3A2,ACSL4,LPCAT3,ALOX15,p-cPLA2/cPLA2) 和CD36的表达. 用铁死抑制剂 (Fer-1) 和CD36过度表达来进行干预.
主要成果:
- 安格II增加了ROS,亡,ET-1,Fe2+,MDA和CD36的表达,同时降低了NO,ZO-1,p-eNOS,VE-cadherin,Occludin和GSH.
- 安格II诱导脂质代谢障碍,改变了与铁亡相关的基因/蛋白质表达,并促进了内皮功能障碍.
- 铁-1治疗挽救了Ang II诱导的HUVEC损伤;CD36过度表达加剧了铁和内皮功能障碍.
结论:
- 安格II通过促进脂质过氧化和改变分子信号的特征,诱导HUVEC损伤和功能障碍.
- CD36在Ang II介导的铁亡和内皮功能障碍中发挥着关键作用.
- 向CD36和铁亡途径为高血压相关的血管并发症提供了潜在的治疗途径.
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