氧化脂PGPC通过通过FABP3促进内皮细胞ferroptosis损害内皮功能
Si Chen1, Jian-Jun Gao1, Yu-Jia Liu1
1Division of Cardiac Surgery, Cardiovascular Diseases Institute, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, NHC Key Laboratory of Assisted Circulation and Vascular Diseases (Sun Yat-sen University), Key Laboratory of Assisted Circulation and Vascular Diseases, Chinese Academy of Medical Sciences, Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, Guangzhou, China.
1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine (PGPC) 诱导内皮细胞中的铁亡,从而损害了血管功能. 这通过CD36受体发生,增加FABP3表达,并为动脉样硬化提供潜在的治疗点.
科学领域:
- 心血管生物学 心血管生物学
- 细胞死亡机制 细胞死亡机制
- 氧化压力是一种氧化压力.
背景情况:
- 铁,一种依赖于铁的细胞死亡,与动脉样硬化有关.
- 脂氧化产物,如PGPC,在动脉样硬化病变中发现.
- PGPC在诱导内皮细胞铁亡中的作用尚不清楚.
研究的目的:
- 调查PGPC是否会诱导内皮细胞铁亡.
- 阐明PGPC影响内皮细胞和血管功能的机制.
- 为了确定动脉样硬化的潜在治疗点.
主要方法:
- 人类静脉内皮细胞 (HUVEC) 用PGPC进行治疗.
- 评估了细胞内铁,脂质过氧化,超氧化离子,谷和线粒体膜潜力.
- 测量了FABP3,GPX4和CD36的表达;对小鼠的大动脉进行了血管扩张测试.
主要成果:
- PGPC增加了铁,脂质过氧化,超氧化离子,FABP3和CD36的表达.
- PGPC降低了GPX4,谷氨和线粒体膜潜能,而费洛斯塔-1.1可以逆转这些效应.
- PGPC损害了血管扩张;铁素-1和FABP3的抑制改善了这种情况.
- CD36和FABP3沉默可以逆转PGPC诱导的影响.
结论:
- 通过CD36受体,PGPC诱导内皮细胞铁,导致FABP3表达的增加.
- 这种铁亡会损害内皮功能和血管扩张,导致动脉样硬化.
- 向CD36-FABP3通路为动脉样硬化症提供了一个新的治疗策略.
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