血管ATGL-依赖性脂解和cPLA-PGI通路的激活可以预防食后内皮功能障碍
M Sternak1, M Stojak2, T Banasik2
1Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Bobrzynskiego 14, Krakow, Poland. magdalena.sternak@jcet.eu.
Cellular and molecular life sciences : CMLS
|March 12, 2024
概括
脂肪三糖 lipase (ATGL) 和脂质滴通过产生前环素 (PGI2) 来保护内皮功能. 抑制ATGL在脂肪饮食后会使内皮功能障碍恶化,突出显示了该通路的血管保护作用.
科学领域:
- 心血管生物学 心血管生物学
- 代谢疾病研究研究
- 内皮细胞功能 内皮细胞功能
背景情况:
- 脂肪三甘油脂酶 (ATGL) 在脂解中起作用,对心脏代谢疾病有影响.
- 虽然经常被认为是有害的,但ATGL诱导的脂解可能具有器官保护作用.
- 脂质滴 (LDs) 和ATGL在调节内皮功能中的特定作用需要详细的描述.
研究的目的:
- 为了研究脂质滴和ATGL介导的脂解在内皮功能调节中的功能.
- 分析ATGL依赖性脂解和细胞质脂酶A2 (cPLA2) 衍生在血管细胞中的eicosanoid生产.
- 评估ATGL依赖的脂解和cPLA2/PGI2途径在食后内皮功能障碍中的体内功能影响.
主要方法:
- 研究了依赖ATGL的LD水解和cPLA2衍生的eicosanoid在动脉,内皮和光滑肌细胞暴露于油酸 (OA) 或酸 (AA) 的产生.
- 在体内对食后内皮功能障碍的功能性影响进行了评估,包括ATGL抑制,cPLA2抑制和前环素 (IP) 受体阻塞.
- 利用ATGL和cPLA2的抑制剂来研究它们对eicosanoid生产和LD积累的影响.
主要成果:
- 与内源性AA衍生的前环素 (PGI2) 产量增加相关的LD形成.
- 抑制ATGL或cPLA2降低了eicosanoid的产生和增加了LDs.
- 在体外,OA的使用损害了内皮屏障的完整性,而ATGL抑制则加剧了这种情况;在体内,橄油诱导的内皮功能障碍因ATGL/cPLA2抑制或IP受体阻塞而恶化.
结论:
- 由外源性脂肪酸刺激的血管LD形成与来自内源性AA的ATGL和cPLA2依赖的PGI2产生有关.
- 在体外,ATGL的抑制会损害内皮质屏障的功能.
- 由脂质过载激活的ATGL-cPLA2-PGI2通路,通过抵消对内皮功能有害影响,发挥血管保护作用.
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