Barlic Jana, Murphy Philip M
Molecular Signaling Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Trends Cardiovasc Med. 2007 Nov;17(8):269-74. doi: 10.1016/j.tcm.2007.09.004.
Recent genetic studies have implicated pro-inflammatory chemokines and chemokine receptors in atherogenesis. Studies at the molecular and cellular levels have suggested specific atherogenic mechanisms for two chemokine-chemokine receptor pairs, CCL2-CCR2 and CX3CL1-CX3CR1, involving differential receptor regulation by the transcription factor peroxisome proliferator-activated receptor gamma. This pathway is triggered by oxidized proatherogenic lipids, such as oxidized low-density lipoprotein and linoleic acid derivatives, which promote differentiation of CCR2(hi)CX3CR1(lo) human monocytes to CCR2(lo)CX3CR1(hi) macrophages that adhere to coronary artery smooth muscle cells in a CX3CR1- and peroxisome proliferator-activated receptor gamma-dependent manner. Switching CX3CR1 on and CCR2 off in vivo may result in cessation of CCR2-dependent migration and activation of CX3CR1-dependent retention that together may promote foam cell accumulation in the vessel wall.
最近的基因研究表明，促炎趋化因子和趋化因子受体与动脉粥样硬化的发生有关。分子和细胞水平的研究揭示了两种趋化因子-趋化因子受体对（CCL2-CCR2和CX3CL1-CX3CR1）特定的致动脉粥样硬化机制，这涉及转录因子过氧化物酶体增殖物激活受体γ对受体的差异性调控。该途径由促动脉粥样硬化的氧化脂质触发，如氧化型低密度脂蛋白和亚油酸衍生物，它们促进CCR2(hi)CX3CR1(lo)人单核细胞分化为CCR2(lo)CX3CR1(hi)巨噬细胞，这些巨噬细胞以CX3CR1和过氧化物酶体增殖物激活受体γ依赖的方式黏附于冠状动脉平滑肌细胞。体内CX3CR1开启而CCR2关闭可能导致CCR2依赖的迁移停止以及CX3CR1依赖的滞留激活，这两者共同作用可能促进血管壁中泡沫细胞的积聚。
