Angiopoietin-like protein 8 accelerates atherosclerosis in ApoE-/- mice
Angiopoietin-like protein 8 accelerates atherosclerosis in ApoE-/- mice
复制标题
血管生成素样蛋白 8 加速 ApoE-/- 小鼠的动脉粥样硬化
DOI：
10.1016/j.atherosclerosis.2020.06.014
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发表时间：
2020-08-01
期刊：
影响因子：
5.3
通讯作者：
Qin, Yanwen
中科院分区：
文献类型：
--
作者：
Jiao, Xiaolu;Yang, Yunyun;Qin, Yanwen
背景和目的：血管生成素样蛋白8（ANGPTL8）是一种参与调节脂质代谢的激素。冠状动脉疾病患者的血浆 ANGPTL8 水平明显高于对照组；然而，ANGPTL8 在动脉粥样硬化中的作用尚未被探索。因此，我们在小鼠模型中探讨了ANGPTL8对动脉粥样硬化发展的影响。方法：我们在ApoE(-/-)小鼠中诱导ANGPTL8敲低实验性动脉粥样硬化。和ANGPTL8过表达ApoE(-/-)小鼠。我们还利用ANGPTL8过表达巨噬细胞探索了这一机制。结果：ANGPTL8表达在人和小鼠动脉粥样硬化病变中增加。 ANGPTL8 过表达促进动脉粥样硬化的发展，而 ANGPTL8 敲低可预防动脉粥样硬化。免疫荧光共染色结果显示ANGPTL8在动脉粥样硬化斑块的巨噬细胞中表达。与野生型细胞相比，ANGPTL8过表达的巨噬细胞，包括骨髓源性巨噬细胞和Raw 264.7巨噬细胞，表现出泡沫细胞形成增强和胆固醇积累增加，这是由胆固醇摄取增加和流出减少引起的。这项研究的结果还表明，ANGPTL8 诱导 CD36 和清道夫受体 (SR)-A 的表达，并抑制 SR-BI 的表达。结论：我们的研究结果表明 ANGPTL8 在动脉粥样硬化的发展和泡沫细胞形成的调节中发挥着意想不到的作用。 ANGPTL8可能是动脉粥样硬化有希望的新靶点。
Background and aims: Angiopoietin-like protein 8 (ANGPTL8) is a hormone involved in regulating lipid metabolism. Patients with coronary artery disease have markedly higher plasma levels of ANGPTL8 than controls; however, the role of ANGPTL8 in atherosclerosis has not been explored. Therefore, we explored the effects of ANGPTL8 on atherosclerosis development in a mouse model.Methods: We induced experimental atherosclerosis in ApoE(-/-) mice ANGPTL8-knockdown. and ANGPTL8-overexpression ApoE(-/-) mice. We also explored the mechanism using ANGPTL8-overexpression macrophages.Results: ANGPTL8 expression was increased in human and mouse atherosclerotic lesions. ANGPTL8 overexpression promoted the development of atherosclerosis whereas ANGPTL8 knockdown protected against atherosclerosis. Immunofluorescence co-staining results showed that ANGPTL8 was expressed in macrophages in atherosclerotic plaques. Compared with wild type cells, ANGPTL8-overexpressing macrophages, including bone marrow-derived macrophages and Raw 264.7 macrophages, showed enhanced foam cell formation and increased accumulation of cholesterol that was induced by increased uptake and decreased effiux of cholesterol. The results of this study also showed that ANGPTL8 induced the expression of CD36 and scavenger receptor (SR)-A, and inhibited the expression of SR-BI.Conclusions: Our findings demonstrate an unanticipated role of ANGPTL8 in the development of atherosclerosis and regulation of foam cell formation. ANGPTL8 may be a promising new target for atherosclerosis.