Ru Ding, Zhiqing He, Lin Zhu, Feng Wu, Feng Zhang, Jiayou Zhang, Yusheng Ren, Min Fan, Chun Liang, Zonggui Wu
Department of Cardiology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
APMIS. 2015 May;123(5):410-21. doi: 10.1111/apm.12362.
High density lipoprotein (HDL) dysfunction has been widely reported in clinic, and oxidation of HDL (ox-HDL) was shown to be one of the most common modifications in vivo and participate in the progression of atherosclerosis. But the behind mechanisms are still elusive. In this study, we firstly analyzed and found strong relationship between serum ox-HDL levels and risk factors of coronary artery diseases in clinic, then the effects of ox-HDL in initiation and progression of atherosclerosis in LDLR knockout mice were investigated by infusion of ox-HDL dissolved in chitosan hydrogel before the formation of lesions in vivo. Several new evidence were shown: (i) the serum levels of ox-HDL peaked early before the formation of lesions in LDLR mice fed with high fat diet similar to oxidative low density lipoprotein, (ii) the formation of atherosclerotic lesions could be accelerated by infusion of ox-HDL, (iii) the pro-atherosclerotic effects of ox-HDL were accompanied by imbalanced levels of effector and regulatory T cells and relative gene expressions, which implied that imbalance of teff and treg might contribute to the pro-atherosclerosis effects of ox-HDL.
高密度脂蛋白（HDL）功能障碍在临床上已被广泛报道，HDL的氧化（ox-HDL）被证明是体内最常见的修饰之一，并参与动脉粥样硬化的进展。但其背后的机制仍不清楚。在本研究中，我们首先分析并发现临床血清ox-HDL水平与冠状动脉疾病危险因素之间存在密切关系，然后通过在体内病变形成前输注溶解于壳聚糖水凝胶中的ox-HDL，研究了ox-HDL对低密度脂蛋白受体敲除小鼠动脉粥样硬化起始和进展的影响。结果显示了几个新的证据：（i）在喂食高脂饮食的LDLR小鼠中，ox-HDL的血清水平在病变形成前早期达到峰值，类似于氧化型低密度脂蛋白；（ii）输注ox-HDL可加速动脉粥样硬化病变的形成；（iii）ox-HDL的促动脉粥样硬化作用伴随着效应T细胞和调节性T细胞水平及相关基因表达的失衡，这意味着teff和treg的失衡可能促成了ox-HDL的促动脉粥样硬化作用。
