C1q/TNF-Related Protein 9 Inhibits THP-1 Macrophage Foam Cell Formation by Enhancing Autophagy.
C1q/TNF-Related Protein 9 Inhibits THP-1 Macrophage Foam Cell Formation by Enhancing Autophagy.
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C1q/TNF 相关蛋白 9 通过增强自噬抑制 THP-1 巨噬细胞泡沫细胞形成
DOI：
10.1097/fjc.0000000000000612
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发表时间：
2018-10
影响因子：
3
通讯作者：
Yu B
中科院分区：
文献类型：
--
作者：
Zhang L;Liu Q;Zhang H;Wang XD;Chen SY;Yang Y;Lv H;Hou JB;Yu B
在早期动脉粥样硬化的发病过程中，脂质巨噬细胞参与斑块的形成和发展。C1q/肿瘤坏死因子相关蛋白-9 （CTRP9）是一种新型脂肪因子，在心血管疾病中具有有益作用。然而，以往的报道尚未研究氧化低密度脂蛋白（ox-LDL）诱导巨噬细胞泡沫细胞的形成是否受CTRP9的影响。根据我们的研究，在ox- ldl诱导的THP-1巨噬细胞中，CTRP9可以减少脂滴数量，降低胆固醇酯（CE）水平，促进胆固醇外排，提高胆固醇转运受体atp结合膜盒转运蛋白A1 （ABCA1）和G1 （ABCG1）的表达水平。此外，ctrp9处理的泡沫细胞通过增强自噬，LC3 II蛋白升高，p62蛋白降低。然而，使用3-甲基腺嘌呤（3-MA）通过抑制自噬来消除CTRP9的作用。在机制上，CTRP9对泡沫细胞的自噬促进作用被AMPK抑制剂化合物C逆转，化合物C抑制腺苷5′-单磷酸腺苷（AMP）活化蛋白激酶(AMPK)/哺乳动物雷帕霉素靶点（mTOR）的信号通路。这些结果表明，CTRP9通过诱导自噬，以AMPK/mTOR信号通路依赖的方式促进胆固醇外流，减少泡沫细胞的形成，从而保护动脉粥样硬化。
During the pathogenesis of early atherosclerosis, lipid-loaded macrophages are involved in plaque development and progression. As a novel adipokine, C1q/tumor necrosis factor–related protein-9 (CTRP9) has beneficial effects in cardiovascular disease. However, previous reports have not studied whether the formation of macrophage foam cell induced by oxidized low-density lipoprotein (ox-LDL) is affected by CTRP9. According to our study, in ox-LDL–induced THP-1 macrophages, CTRP9 could reduce the quantity of lipid droplets, lower the level of cholesteryl ester (CE), promote cholesterol efflux, as well as increase the expression level of the cholesterol transport receptors ATP-binding membrane cassette transporter A1 (ABCA1) and G1 (ABCG1). In addition, the protein of LC3 II is elevated and that of p62 is decreased in CTRP9-treated foam cells by enhancing autophagy. However, using 3-methyladenine (3-MA) abolished the role of CTRP9 by inhibiting autophagy. Mechanistically, the autophagy-promoting effects of CTRP9 on foam cells was reversed by an AMPK inhibitor, Compound C, which inhibited the signaling pathway of adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR). These results show that CTRP9 protects against atherosclerosis by promoting cholesterol efflux to reduce the formation of foam cell in virtue of inducing autophagy in an AMPK/mTOR signaling pathway–dependent manner.