Oleoylethanolamide stabilizes atherosclerotic plaque through regulating macrophage polarization via AMPK-PPARα pathway
Oleoylethanolamide stabilizes atherosclerotic plaque through regulating macrophage polarization via AMPK-PPARα pathway
复制标题
油酰乙醇酰胺通过 AMPK-PPAR α 途径调节巨噬细胞极化来稳定动脉粥样硬化斑块
DOI：
10.1016/j.bbrc.2020.01.103
复制
发表时间：
2020-04-02
影响因子：
3.1
通讯作者：
Wang, Yiqing
中科院分区：
文献类型：
--
作者：
Chen, Zhengdong;Zhuo, Rengong;Wang, Yiqing
背景资料：动脉粥样硬化斑块破裂是急性心血管危险事件的主要触发因素，操纵M1/M2巨噬细胞稳态是调节动脉粥样硬化斑块稳定性的有效策略。方法：用油酰乙醇胺（OEA）处理THP-1来源的巨噬细胞，然后用LPS/IFN-γ处理，用Western blot、实时荧光定量PCR和免疫荧光染色检测M1、M2巨噬细胞标志物的变化。采用免疫荧光染色和western blot检测OEA对载脂蛋白E（ApoE）（-/-）小鼠主动脉弓巨噬细胞极化的影响，并采用Masson三色染色和苏木精-伊红（HE）染色检测斑块稳定性。OEA处理增强了两个经典的M2巨噬细胞标志物，巨噬细胞甘露糖受体（CD 206）和转化生长因子的表达在THP-1衍生的巨噬细胞中，诱导型一氧化氮合酶（M1巨噬细胞）的表达降低。使用siRNA阻断PPAR α和通过其抑制剂化合物C抑制AMP活化蛋白激酶（AMPK）减弱了M2巨噬细胞标志物的OEA诱导的表达。结论：OEA通过AMPK-PPAR α途径调节巨噬细胞的极化，从而改善动脉粥样硬化斑块的稳定性。(C)2020由Elsevier Inc.出版。
Background: Atherosclerotic plaque rupture is the major trigger of acute cardiovascular risk events, and manipulation of M1/M2 macrophage homeostasis is an effective strategy for regulating atherosclerotic plaque stability. This study was aimed to illuminate the effects of oleoylethanolamide (OEA) on macrophage polarization and plaque stability.Methods: Macrophages derived from THP-1 were treated with OEA followed by LPS/IFN-gamma, and the markers of M1, M2 macrophages were monitored by western blot, real-time PCR and immunofluorescence staining. The effect of OEA on macrophage polarization in the arch of aortic arteries was tested by immunofluorescence staining and western blot, and the plaque stability was completed by Masson's trichrome and hematoxylin and eosin (HE) in apolipoprotein E (ApoE)(-/-) mice.Results: OEA treatment enhanced the expression of two classic M2 macrophage markers, macrophage mannose receptor (CD206) and transforming growth factor (TGF-beta), while the expression of iNOS (M1 macrophages) was decreased in THP-1-derived macrophages. Blocking of PPAR alpha using siRNA and inhibition of AMP-activated protein kinase (AMPK) by its inhibitor compound C attenuated the OEA-induced expression of M2 macrophage markers. In addition, OEA significantly suppressed M1, promoted M2 macrophage polarization, increased collagen content and decreased necrotic core size in atherosclerotic plaques in ApoE(-/-) mice, which were linked with the expression of PPAR alpha.Conclusions: OEA improved atherosclerotic plaque stability through regulating macrophage polarization via AMPK-PPAR alpha pathway. (C) 2020 Published by Elsevier Inc.