Liu Jian, Huang Haoyue, Shi Sheng, Wang Xu, Yu Yunsheng, Hu Yanqiu, Sun Jiacheng, Ren Chuanlu, Yang Junjie, Shen Zhenya
Department of Cardiovascular Surgery, The First Affiliated Hospital and Institute for Cardiovascular Science, Soochow University, Suzhou, Jiangsu 215006, P.R. China.
Department of Cardiovascular Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, P.R. China.
Exp Ther Med. 2018 Nov;16(5):3785-3792. doi: 10.3892/etm.2018.6694. Epub 2018 Sep 4.
Apolipoprotein M (apoM) is a recently identified human apolipoprotein that is associated with the formation of high-density lipoprotein (HDL). Studies have demonstrated that statins may affect the expression of apoM; however, the regulatory effects of statins on apoM are controversial. Furthermore, the underlying mechanisms by which statins regulate apoM remain unclear. In the present study, and models were used to investigate whether the anti-atherosclerotic effects of statins are associated with its apoM-regulating effects and the underlying mechanism. Hyperlipidemia was induced by in apolipoprotein E-deficient mice by providing a high-fat diet. Atorvastatin was administered to hyperlipidemic mice and HepG2 cells to investigate its effect on apoM expression. The liver X receptor α (LXRα) agonist T0901317 was also administered together with atorvastatin to hyperlipidemic mice and HepG2 cells. The results revealed that atorvastatin increased apoM expression, which was accompanied with decreased expression of LXRα in the liver of hyperlipidemic apolipoprotein E-deficient mice and HepG2 cells. Additionally, apoM upregulation was inhibited following treatment with T0901317. In summary, atorvastatin exhibited anti-atherosclerotic effects by upregulating apoM expression in hyperlipidemic mice, which may be mediated by the inhibition of LXRα.
载脂蛋白M（apoM）是一种最近发现的人类载脂蛋白，与高密度脂蛋白（HDL）的形成有关。研究表明，他汀类药物可能会影响apoM的表达；然而，他汀类药物对apoM的调节作用存在争议。此外，他汀类药物调节apoM的潜在机制仍不清楚。在本研究中，使用载脂蛋白E缺陷小鼠和HepG2细胞模型来研究他汀类药物的抗动脉粥样硬化作用是否与其对apoM的调节作用及其潜在机制有关。通过给载脂蛋白E缺陷小鼠提供高脂饮食诱导高脂血症。将阿托伐他汀给予高脂血症小鼠和HepG2细胞，以研究其对apoM表达的影响。还将肝脏X受体α（LXRα）激动剂T0901317与阿托伐他汀一起给予高脂血症小鼠和HepG2细胞。结果显示，阿托伐他汀增加了apoM的表达，这伴随着高脂血症载脂蛋白E缺陷小鼠肝脏和HepG2细胞中LXRα表达的降低。此外，用T0901317处理后，apoM的上调受到抑制。总之，阿托伐他汀通过上调高脂血症小鼠的apoM表达发挥抗动脉粥样硬化作用，这可能是由LXRα的抑制介导的。
