Kong Jie, Wang Feng, Zhang Jianbin, Cui Yiyao, Pan Lin, Zhang Wenjian, Wen Jianyan, Liu Peng
Department of Cardiovascular Surgery, China-Japan Friendship Hospital, Beijing, China; Graduate School of Peking Union Medical College, Beijing, China.
Department of Cardiovascular Surgery, China-Japan Friendship Hospital, Beijing, China.
J Surg Res. 2018 Dec;232:398-407. doi: 10.1016/j.jss.2018.06.066. Epub 2018 Jul 19.
Exosomes released from endothelial progenitor cells (EPCs) play a protective role in various disease models. Both endothelial cell (EC) damage and smooth muscle cell (SMC) proliferation are involved in the pathological process of restenosis after angioplasty and stenting. Few studies have focused on the therapeutic role of exosomes in EC damage and SMC proliferation. In this study, we sought to investigate the effect of exosomes released by human fetal aorta-derived EPCs on the rat carotid artery balloon injury model in vivo. We also sought to determine the effect of exosomes on both ECs and SMCs in vitro.
Exosomes (Exo group) or saline (Con group) were injected in rat carotid balloon injury model animals. The rats were sacrificed after 2, 4, 14, and 28 d, and injured carotid specimens were collected for Evans blue staining, hematoxylin-eosin staining, and immunohistochemistry.
When the Con group and the Exo group were compared, the reendothelialized areas were not significantly different after 2 or 4 d, as shown by Evans blue staining. The hematoxylin-eosin results showed that the intimal to medial area ratio was slightly but not significantly higher in the Exo group after 2 and 4 d. The immunohistochemistry results showed that the proliferation of SMCs was slightly higher in the Exo group after 2 and 4 d, but the difference was not significant. The reendothelialization area of the Con group was significantly smaller than that of the Exo group at day 14. Both the intimal to medial area ratio and SMC proliferation in the Exo group were significantly smaller than those of the Con group at 14 or 28 d. In the in vitro study, exosome treatment significantly enhanced the proliferation and migration of both ECs and SMCs.
Exosomes derived from EPCs could inhibit neointimal hyperplasia after carotid artery injury in rats. The protective effect of exosomes may manifest through the promotion of EC repair rather than direct suppression of proliferation and migration of smooth muscles cells.
内皮祖细胞（EPCs）释放的外泌体在多种疾病模型中发挥保护作用。内皮细胞（EC）损伤和平滑肌细胞（SMC）增殖均参与血管成形术和支架置入术后再狭窄的病理过程。很少有研究关注外泌体在EC损伤和SMC增殖中的治疗作用。在本研究中，我们试图研究人胎主动脉来源的EPCs释放的外泌体对体内大鼠颈动脉球囊损伤模型的影响。我们还试图确定外泌体在体外对ECs和SMCs的影响。
将外泌体（外泌体组）或生理盐水（对照组）注射到大鼠颈动脉球囊损伤模型动物体内。在2、4、14和28天后处死大鼠，收集损伤的颈动脉标本进行伊文思蓝染色、苏木精-伊红染色和免疫组织化学分析。
伊文思蓝染色显示，比较对照组和外泌体组，2天或4天后再内皮化区域无显著差异。苏木精-伊红染色结果显示，2天和4天后外泌体组内膜与中膜面积比略高，但无显著差异。免疫组织化学结果显示，2天和4天后外泌体组SMC增殖略高，但差异不显著。14天时，对照组的再内皮化面积显著小于外泌体组。14天或28天时，外泌体组的内膜与中膜面积比和SMC增殖均显著小于对照组。在体外研究中，外泌体处理显著增强了ECs和SMCs的增殖和迁移。
EPCs来源的外泌体可抑制大鼠颈动脉损伤后的内膜增生。外泌体的保护作用可能通过促进EC修复而非直接抑制平滑肌细胞的增殖和迁移来体现。
