先天免疫RIG-I信号通路与动脉粥样硬化的研究

The accumulation of oxidized cholesterol is one of factors to influence the formation of foam cells, while atherosclerosis is affected by multiple stresses. Recently, the effect of innate immunity on atherosclerosis has been gained a great attention. Innate immunity promoters atherosclerosis mainly by its inflammatory signaling which further induces the formation of foam cells. Our pervious paper demonstrated that oxidized cholesterol could induce the expression of RIG-I which is also highly expressed in human case and animal model, and that RIG-I/MAVS pathway mediated inflammation in atherosclerosis. We now find in MAVS and ApoE gene double knocked out mice, that atherosclerosis alleviates and the expression of cholesterol efflux genes ABCA1 and ABCG1 are elevated, indicating that RIG-I/MAVS pathway may cross talk with cholesterol metablic pathway. Therefore, we propose this project to study the relationship of RIG-I pathway and cholesterol metablism.

氧化型胆固醇在巨噬细胞的累积是形成泡沫细胞的重要因素之一。动脉粥样硬化的形成也受到许多因素的影响。近年来先天免疫对动脉粥样硬化的影响受到关注。先天免疫对动脉粥样硬化的影响主要是其介导的炎症反应。这些炎症反应会促进泡沫细胞的形成。我们前期发表的文章证明氧化型胆固醇可以诱导先天免疫分子RIG-I的表达，在动脉粥样硬化的病人和小鼠模型中都呈现中高表达。RIG-I/MAVS信号通路介导了动脉粥样硬化的炎症反应。进一步的研究发现，在MAVS-/-Apoe-/-基因双敲小鼠的动脉粥样硬化模型中，动脉粥样硬化明显减轻。同时发现胆固醇运转的基因ABCA1和ABCG1表达水平异常高，这提示RIG-I/MAVS信号通路可能与胆固醇代谢有关。为此，我们提出本课题，来揭示先天免疫RIG-I信号通路与胆固醇代谢的关系，进一步研究这种联系是否影响动脉粥样硬化的形成。