Wen Wen, He Ming, Liang Xiao, Gao Shan-shan, Zhou Juan, Yuan Zu-yi
a Department of Cardiovascular Medicine and.
b Department of Rheumatology, First Affiliated Hospital of Medical School , Xi'an Jiaotong University , Shaanxi , PR China , and.
Autoimmunity. 2016;49(2):115-23. doi: 10.3109/08916934.2015.1118761. Epub 2016 Mar 8.
Atherosclerosis characterized by accumulation of foam cells in the arterial intimal layer is accelerated in rheumatoid arthritis (RA) patients. We and others have previously demonstrated that serum from RA patients and collagen-induced arthritis (CIA) mice had proatherogenic features that might lead to progression of atherosclerosis. Here we further examined the effects of serum from CIA mice on the transformation of macrophage-derived foam cells, and investigated potential mechanism.
DBA/1j mice were used to establish CIA model. Murine peritoneal macrophages and macrophage cell line RAW264.7 were treated with different dilute concentrations of mice serum.
CIA mice serum increased cholesterol influx and accumulation in murine macrophages, and markedly up-regulated scavenger receptor CD36 expression in the cells, but had no effect on intracellular lipid efflux. Neutralizing monocyte chemotactic protein (MCP)-1, the most significant altered cytokine we observed between normal and CIA mice serum to CIA mice could not reverse these effects. However, administering simvastatin to CIA mice could lower high-density lipoprotein-cholesterol (HDL-C) level and elevate oxidized low-density lipoprotein (ox-LDL) level in CIA mice serum, with attendant decreased lipid accumulation as well as CD36 expression in murine macrophages.
Accelerated transformation of macrophage-derived foam cells via up-regulated CD36 expression is related to dyslipidemia rather than elevated inflammatory factor MCP-1 level in CIA mice serum. Decreased HDL-C and higher ox-LDL levels in CIA mice serum may link RA to atherosclerosis.
类风湿关节炎（RA）患者动脉内膜层中泡沫细胞的积累会加速动脉粥样硬化。我们和其他人之前已经证明，RA患者和胶原诱导性关节炎（CIA）小鼠的血清具有促动脉粥样硬化特征，可能导致动脉粥样硬化进展。在此，我们进一步研究了CIA小鼠血清对巨噬细胞源性泡沫细胞转化的影响，并探讨了潜在机制。
使用DBA/1j小鼠建立CIA模型。用不同稀释浓度的小鼠血清处理小鼠腹腔巨噬细胞和巨噬细胞系RAW264.7。
CIA小鼠血清增加了小鼠巨噬细胞中胆固醇的流入和积累，并显著上调了细胞中清道夫受体CD36的表达，但对细胞内脂质流出没有影响。中和单核细胞趋化蛋白（MCP）-1（我们观察到的正常小鼠血清和CIA小鼠血清之间变化最显著的细胞因子）对CIA小鼠没有逆转这些作用。然而，给CIA小鼠服用辛伐他汀可以降低CIA小鼠血清中的高密度脂蛋白胆固醇（HDL-C）水平，升高氧化低密度脂蛋白（ox-LDL）水平，同时减少小鼠巨噬细胞中的脂质积累以及CD36表达。
通过上调CD36表达加速巨噬细胞源性泡沫细胞的转化与血脂异常有关，而不是与CIA小鼠血清中炎症因子MCP-1水平升高有关。CIA小鼠血清中HDL-C降低和ox-LDL水平升高可能将RA与动脉粥样硬化联系起来。
