Department of Traditional Chinese Medicine, Nan fang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, 510515, Guangdong, China.
Cell Stress Chaperones. 2013 Sep;18(5):643-52. doi: 10.1007/s12192-013-0417-z. Epub 2013 Mar 15.
As a new potential inflammatory mediator, visfatin plays an important role in inflammation and atherosclerosis. The formation of macrophage-derived foam cells occurs at the early stage of atherosclerosis and underlies the visible fatty streak. Recent studies have indicated that visfatin may be associated with the development of foam cells, but its exact effect and molecular mechanism remain unknown. This study aims to study the effect of visfatin on foamy cell formation and its underlying molecular mechanism. Visfatin levels were determined in apolipoprotein E (ApoE) knockout (KO) mice on a western diet for 16 weeks. Effects of visfatin in cholesterol accumulation were studied both in vivo and in vitro. The levels of scavenger receptors located in macrophage surface were measured in RAW264.7 cells after treatment with visfatin. Visfatin levels were much higher in ApoE KO mice than that in the control mice. Meanwhile, oxidized low-density lipoprotein induces both visfatin release from RAW264.7 cells and its cellular levels within 24 h. Visfatin promotes lipid accumulation mainly through excessive cholesterol uptake not only in RAW264.7 cells but also in peritoneal macrophages isolated from ApoE KO mice. Furthermore, visfatin induces the activation of scavenger receptors (SR)-A and cluster of differentiation (CD)36, but not that of SR-BI, ATP-binding cassette transporter (ABC)A1, or ABCG1 in RAW264.7 cells. Both transcriptional and posttranscriptional regulation may work in concert to mediate the expression of SR-A and CD36 in visfatin-treated cells. Visfatin induces cholesterol accumulation in macrophages and accelerates the process of atherosclerosis mainly through modulating the expression of SR-A and CD36.
作为一种新的潜在炎症介质，内脂素在炎症和动脉粥样硬化中发挥重要作用。巨噬细胞源性泡沫细胞的形成发生在动脉粥样硬化的早期，是可见的脂肪条纹的基础。最近的研究表明，内脂素可能与泡沫细胞的形成有关，但确切的作用及其分子机制尚不清楚。本研究旨在研究内脂素对泡沫细胞形成的影响及其潜在的分子机制。在给予西方饮食 16 周的载脂蛋白 E（ApoE）基因敲除（KO）小鼠中测定内脂素水平。在体内和体外研究内脂素对胆固醇积累的影响。用内脂素处理 RAW264.7 细胞后，测量巨噬细胞表面的清道夫受体水平。apoE KO 小鼠的内脂素水平明显高于对照组。同时，氧化型低密度脂蛋白在 24 小时内诱导 RAW264.7 细胞释放内脂素及其细胞内水平。内脂素不仅在 RAW264.7 细胞中，而且在从 apoE KO 小鼠分离的腹腔巨噬细胞中，主要通过过量摄取胆固醇促进脂质积累。此外，内脂素诱导清道夫受体（SR）-A 和分化簇（CD）36 的激活，但不诱导 SR-BI、三磷酸腺苷结合盒转运体（ABC）A1 或 ABCG1 的激活。转录和转录后调节可能协同作用，调节内脂素处理细胞中 SR-A 和 CD36 的表达。内脂素通过调节 SR-A 和 CD36 的表达，诱导巨噬细胞内胆固醇积累，并加速动脉粥样硬化的进程。
