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在M1和M2巨细胞中,PACAP调节VPAC1表达,炎症过程和脂质稳态

Roman Witzel¹, Annika Block¹, Solvey Pollmann¹

¹Department of Medical Cell Biology, Institute of Anatomy and Cell Biology, Philipps-University of Marburg, Marburg, Germany.

Frontiers in cardiovascular medicine

|October 30, 2023

概括

垂体腺酸环酶激活多 (PACAP) 缺乏会通过影响巨细胞炎症和脂质代谢而加剧动脉样硬化. PACAP和VPAC1信号传递是关键的调节器,这表明它们在预防动脉样硬化方面具有潜在的治疗作用.

科学领域:

心血管研究研究心血管研究
免疫学免疫学免疫学
内分泌学在内分泌学.

背景情况:

pituitary adenylate cyclase-activating polypeptide (PACAP) 是一种参与细胞保护,炎症和心血管调节的抗atherogenic神经.
了解PACAP在巨细胞亚型中的作用对于其在动脉样硬化中的治疗潜力至关重要.

研究的目的:

研究PACAP及其受体VPAC1对不同巨细胞 (MΦ) 亚型的炎症过程和脂质稳态的调节作用.
评估PACAP缺乏对动脉样硬化发展的影响,体内和体外.

主要方法:

在体内进行动脉样硬化研究的PACAP-/-/ApoE-/-小鼠的生成.
在体外实验中将骨髓衍生巨细胞 (BMDM) 和THP-1细胞分化为M1/M2亚型.
对光膜狭窄,巨标记物,脂质吸收 (oxLDL),基因表达,蛋白质水平和细胞因子释放的分析.

主要成果:

PACAP-/-/ApoE-/-小鼠在动脉样硬化斑块中表现出增加的光膜狭窄和改变的巨细胞标记物表达 (VPAC1,CD86,CD163).
在体外,PACAP缺乏改变了MΦ亚型中的VPAC1水平,TNF-α表达和脂质滴积.
VPAC1抗剂增加了oxLDL的吸收,而激动剂降低了THP-1细胞中的细胞内甘油三.

结论:

通过VPAC1信号传递作用的PACAP显著调节巨细胞中的炎症过程和脂质平衡,影响泡细胞的形成.
PACAP和VPAC1激动剂显示出作为新型抗动脉增生疗法的前景.

关键词:

这就是PacaPap的意义.在VPAC1中使用.动脉样硬化动脉样硬化这是一种炎症炎症炎症炎症.巨细胞是什么?巨细胞是什么?oxLDL oxLDL 的意思是什么?

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