EPAS1通过内皮脂肪酸吸收减轻动脉样硬化在受损的流动部位的启动
Daniela Pirri1,2, Siyu Tian1,3, Blanca Tardajos-Ayllon3
1School of Medicine and Population Health, INSIGNEO Institute, and the Bateson Centre (D.P., S.T., S.E.I., J.S.-C.), University of Sheffield, United Kingdom.
Circulation research
|September 5, 2024
概括
内皮EPAS1 (HIF2A) 通过促进EC增殖和脂肪酸代谢来保护对动脉样硬化. 肥胖会损害这种途径,这表明血管功能障碍的新治疗点.
科学领域:
- 心血管生物学 心血管生物学
- 内皮细胞功能 内皮细胞功能
- 动脉样硬化病原体的产生
背景情况:
- 干扰血液流动会导致内皮细胞 (EC) 功能障碍和动脉样硬化斑块的不均形成.
- 肥胖会使动脉样硬化恶化,但涉及ECs的分子机制仍然不清楚.
- 转录因子EPAS1 (HIF2A) 已知具有内皮作用,但其与动脉样硬化的联系尚未探索.
研究的目的:
- 研究EPAS1在内皮中对肥胖和动脉样硬化的作用.
- 阐明在动脉样硬化中链接EPAS1,肥胖和EC功能障碍的分子机制.
主要方法:
- 在实验室中分析了EC对剪切应力的反应,并在体内进行了流动干扰.
- 在使用高脂肪饮食或勒丁基因缺失的小鼠中诱导肥胖和脂质失调.
- 在高胆固醇贫血小鼠中通过诱导性内皮缺失评估EPAS1的作用.
主要成果:
- EPAS1在易发生动脉样硬化的流动干扰部位被丰富.
- 肥胖小鼠显示内皮质EPAS1降低;硫福拉恢复了EPAS1并降低了甘油三.
- 内皮的EPAS1删除加剧了动脉样硬化,表明通过脂肪酸代谢 (CD36,LIPG) 发挥了动脉样保护作用.
结论:
- 内皮EPAS1通过脂肪酸处理维持EC增殖来减轻动脉样硬化.
- 肥胖抑制了这种修复途径,通过三糖-PHD2介导的EPAS1.1抑制.
- 研究结果表明,与肥胖相关的血管功能障碍有新的治疗点.
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