Lipoxin A4 and its analog attenuate high fat diet-induced atherosclerosis via Keap1/Nrf2 pathway.
Lipoxin A4 and its analog attenuate high fat diet-induced atherosclerosis via Keap1/Nrf2 pathway.
复制标题
DOI：
10.1016/j.yexcr.2022.113025
复制
发表时间：
2022-01
影响因子：
3.7
通讯作者：
Fen Xu;Jiamin Zhang;Xiao-yan Zhou;Hua Hao
中科院分区：
文献类型：
--
作者：
Fen Xu;Jiamin Zhang;Xiao-yan Zhou;Hua Hao
巨噬细胞过度氧化应激和抗氧化能力下降是导致巨噬细胞向泡沫细胞转化的初始因素，这是动脉粥样硬化（AS）进展的关键事件。BML-111是脂氧素A4（LXA 4）的类似物，通过激活NF-E2相关因子2（Nrf 2）强烈减弱高脂（HF）饮食诱导的动脉粥样硬化。然而，这种作用不是通过特异性LXA 4受体（甲酰肽受体2，FPR 2）。BML-111还能显著抑制HF饲料引起的主动脉MDA水平升高，HDL水平升高，IL-1、MCP-1、IL-6、VCAM、ICAM和TNF-α水平降低。在体外实验中，LXA 4通过Nrf 2途径抑制THP-1细胞向泡沫细胞转化。本研究结果表明LXA 4及其类似物对HF诱导的SD大鼠AS有预防作用，其机制可能是通过Keap 1/Nrf 2通路实现的。
Excessive oxidative stress and decreased antioxidant capacity of macrophages are initial factors which cause macrophages to transform to foam cells, which represents a key event in the progression of atherosclerosis (AS). BML-111, the analog of lipoxin A4(LXA4) strongly attenuated high fat (HF) diet-induced atherosclerosis by activating NF-E2 related factor 2 (Nrf2). However, the effect was not through a specific LXA4receptor (formyl peptide receptor 2, FPR2). BML-111 also strongly inhibited HF diet-induced promotion of MDA level, increased HDL level and decreased IL-1, MCP-1, IL-6, VCAM, ICAM and TNF-α level in aorta. In thein vitroexperiments, LXA4inhibited THP-1 cells to transform to foam cellsviaNrf2 pathway. Our findings demonstrated that LXA4and its analog prevented AS induced by HF diet in SD rats, under which the possible mechanism is through Keap1/Nrf2 pathway.