油酰乙醇胺通过 AMPK-PPARα 通路调节巨噬细胞极化稳定动脉粥样硬化斑块。
Oleoylethanolamide stabilizes atherosclerotic plaque through regulating macrophage polarization via AMPK-PPARα pathway.
机构信息
Xiamen Key Laboratory of Chiral Drugs, Medical College, Xiamen University, Xiamen, China; Xiamen University Affiliated Zhongshan Hospital, Xiamen, China.
Xiamen Key Laboratory of Chiral Drugs, Medical College, Xiamen University, Xiamen, China.
出版信息
Biochem Biophys Res Commun. 2020 Apr 2;524(2):308-316. doi: 10.1016/j.bbrc.2020.01.103. Epub 2020 Jan 25.
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-γ, 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-β), while the expression of iNOS (M1 macrophages) was decreased in THP-1-derived macrophages. Blocking of PPARα 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 PPARα.
CONCLUSIONS
OEA improved atherosclerotic plaque stability through regulating macrophage polarization via AMPK-PPARα pathway.
背景
动脉粥样硬化斑块破裂是急性心血管风险事件的主要触发因素，调节 M1/M2 巨噬细胞动态平衡是调节动脉粥样硬化斑块稳定性的有效策略。本研究旨在阐明油酰乙醇酰胺（OEA）对巨噬细胞极化和斑块稳定性的影响。
方法
用 OEA 处理 THP-1 衍生的巨噬细胞，然后用 LPS/IFN-γ处理，通过 Western blot、实时 PCR 和免疫荧光染色监测 M1、M2 巨噬细胞的标志物。通过免疫荧光染色和 Western blot 检测 OEA 对主动脉弓巨噬细胞极化的影响，并通过 Masson 三色和苏木精和伊红（HE）染色检测载脂蛋白 E（ApoE）小鼠的斑块稳定性。
结果
OEA 处理增强了两种经典 M2 巨噬细胞标志物，即巨噬细胞甘露糖受体（CD206）和转化生长因子（TGF-β）的表达，而 THP-1 衍生巨噬细胞中 iNOS（M1 巨噬细胞）的表达减少。用 siRNA 阻断 PPARα和用其抑制剂化合物 C 抑制 AMP 激活的蛋白激酶（AMPK）减弱了 OEA 诱导的 M2 巨噬细胞标志物的表达。此外，OEA 显著抑制 M1，促进 M2 巨噬细胞极化，增加 ApoE 小鼠动脉粥样硬化斑块中的胶原含量，减少坏死核心大小，与 PPARα的表达有关。
结论
OEA 通过 AMPK-PPARα 通路调节巨噬细胞极化改善动脉粥样硬化斑块稳定性。
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