动脉损伤后引发的血管再狭窄是导致心血管病术后失败的重要原因。近年来研究提示除了血管壁内细胞参与再狭窄形成外，巨噬细胞（MΦ）在损伤后的血管重构中也发挥了重要作用。然而对于MΦ如何协同参与血管重构知之甚少。我们前期研究发现损伤动脉中过度凋亡的平滑肌细胞（VSMC）通过上调MCP-1激活MΦ，而后者可分泌含miR-126的微泡；同时还发现凋亡的VSMC内SDF-1表达上调、外膜FB增殖以及内皮修复加快。因此，我们推测动脉损伤诱发VSMC的凋亡，释放MCP-1活化MΦ，后者分泌富含miR-126的微泡诱导VSMC释放SDF-1作用于外膜FB参与促进内皮修复。本课题拟利用分子生物学手段研究MΦ内miR-126对FB的生物学影响，并利用靶基因报告系统检测miR-126的靶标蛋白；通过颈动脉损伤和过表达miR-126 mimic或antagomir来验证我们的推测，完善动脉损伤后血管重构假说。

Restenosis, a major result of arterial injury, is a significant hindrance to the long-term success of surgery administered to dealing with cardiovascular diseases. Most research indicates that multiple vessel cells participate in the process of restenosis. Recently more studies illustrate that macrophages are also involved in vessel remodeling. Nonetheless, how macrophages synergize the remodeling remains unclear. Our previous data showed that excessive apoptotic vessel smooth muscle cells(VSMC) in injured artery could activate macrophages through upregulating MCP-1 and activate macrophages which excreted microvesicles containing miR-126. Meanwhile SDF-1 in apoptotic VSMC was upregulated as well, accompanying with proliferation of adventitial fibroblasts(FB) and accelerated repair of endothelial layer. Therefore, we hypothesize that arterial injury trigger VSMC apoptosis to induce MCP-1 for activating macrophages which in turn parent microvesicles holding miR-126 and deliver these microvesicles to VSMC for SDF-1 production to signal adventitial FB to stimulate re-endothelialization in vessel remodeling. The current proposal will test the biological behavior of adventitial FB primed by miR-126 and validate miR-126 target using a luciferase reporter system. In addition, we will further our hypothesis through animal model plus over-expressing miR-126 mimic and antagomir to consummate the vessel remodeling hypothesis.

动脉损伤后引发的血管再狭窄是导致心血管病术后失败的重要原因。近年来研究发现巨噬细胞对于血管重构也有重要作用，但其具体机制尚不明朗。前期研究中我们发现损伤动脉中 过度凋亡的平滑肌细胞（VSMC）通过上调MCP-1激活巨噬细胞，而后者可分泌含miR-126的微泡 ；同时还发现凋亡的VSMC内SDF-1表达上调、外膜FB增殖以及内皮修复加快。因此本课题设想巨噬细胞是通过含miR-126的微泡诱导VSM C释放SDF-1作用于外膜FB参与促进内皮修复。本课题利用了分子生物学手段研究巨噬细胞内miR -126对FB的生物学影响，检测了miR-126的靶标蛋白；通过颈动脉损伤和过表达miR-126 mimic或antagomir来验证我们的推测，完善动脉损伤后血管重构假说。