miR-296-5p在动脉粥样硬化（As）斑块进展期高表达，但其在As中的作用及机制尚不清楚。前期我们采用生物信息学及预实验发现miR-296-5p可靶向抑制过氧化物酶体增殖物激活受体δ（PPARδ），而PPARδ可调控巨噬细胞极性表型转换，进而影响As进程。为此本项目拟采用报告基因系统深入探讨miR-296-5p与PPARδ的直接作用和结合位点；体外实验观察miR-296-5p对巨噬细胞极性表型、炎症因子的释放和PPARδ表达的影响；进一步探讨PPARδ在miR-296-5p促巨噬细胞极性表型转换的作用；建立As动物模型，整体水平观察miR-296-5p对斑块进程、巨噬细胞极性、PPARδ表达和体内炎症水平的影响。项目的研究有望揭示miR-296-5p靶向沉默PPARδ、促进巨噬细胞极性表型转换及在As中的作用和分子机制，为体内调控巨噬细胞极性表型和抗As提供新的干预途径和药物作用靶点。

MiR-296-5p is highly expressed in the progressive of atherosclerotic plaque, but its roles and mechanisms in atherosclerosis are still not clear. Previously through bioinformatics and preliminary experiments we have found that miR-296-5p inhibited peroxisome proliferator activated receptor delta (PPARδ) targetedly, which plays an important role in modulating macrophage polarization phenotype transformation and thereby affecting the process of atherosclerosis. To this end, the project will investigate more deeply on the direct effects and binding sites of miR-296-5p to PPARδ by report gene systems. In vitro experiments observe the effects of miR-296-5p on the macrophage polarization phenotype, inflammatory cytokine release and PPARδ expression. Furthermore, we investigate the roles of PPARδ on miR-296-5p regulating macrophage polarization phenotype transformation. Finally, we evaluate the regulatory role of miR-296-5p on plaque progression, macrophage polarization and the level of inflammation in vivo at systematic level. The launch of the project will reveal the effects and molecular mechanisms of mir-296-5p targeted inhibition PPARδ, promote macrophage polarization phenotype transformation and atherosclerosis, and provide new intervention avenues and drug targets for in vivo regulation of macrophage polarization phenotype and anti-atherosclerosis as well.