Prostaglandin I2 Promotes Recruitment of Endothelial Progenitor Cells and Limits Vascular Remodeling
Prostaglandin I2 Promotes Recruitment of Endothelial Progenitor Cells and Limits Vascular Remodeling
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DOI：
10.1161/atvbaha.109.193730
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发表时间：
2010-03-01
影响因子：
8.7
通讯作者：
Ushikubi, Fumitaka
中科院分区：
文献类型：
--
作者：
Kawabe, Jun-ichi;Yuhki, Koh-ichi;Ushikubi, Fumitaka
目的：内皮祖细胞通过参与限制血管重塑的再内皮化，在血管损伤的自我修复中发挥重要作用。方法和结果：从野生型(WT)小鼠或缺乏前列腺素I-2受体IP的小鼠(IP-/-小鼠)的骨髓(BM)中分离出EPC(LIN(-)cKit(+)Flk-1(+)细胞)。逆转录-聚合酶链式反应分析表明，骨髓细胞中的EPC特异性表达IP。与WT EPC相比，IP缺乏的EPC的细胞特性、对纤维连接蛋白的黏附、迁移和增殖显著减弱。相反，IP激动剂促进了WT EPC的这些功能，但在IP缺乏的EPC中则没有。通过将IP-/-小鼠的BM细胞移植到WT小鼠身上，BM细胞中IP的特异性缺失加速了钢丝损伤介导的股动脉新生内膜的形成。值得注意的是，输注的WT内皮祖细胞，而不是IP缺陷的内皮祖细胞，被招募到损伤的血管中，参与血管内皮化，并有效地挽救了加速的血管重建。结论：这些发现清楚地表明，前列腺素I-2-IP系统是内皮细胞完成其功能所必需的，并在血管重建的调节中发挥关键作用。(动脉血栓血管生物)2010；30：464-470。)
Objective-Endothelial progenitor cells (EPCs) play an important role in the self-healing of a vascular injury by participating in the reendothelialization that limits vascular remodeling. We evaluated whether prostaglandin I-2 plays a role in the regulation of the function of EPCs to limit vascular remodeling.Methods and Results-EPCs (Lin(-)cKit(+)Flk-1(+) cells) were isolated from the bone marrow (BM) of wild-type (WT) mice or mice lacking the prostaglandin I-2 receptor IP (IP-/- mice). Reverse transcription-polymerase chain reaction analysis showed that EPCs among BM cells specifically express IP. The cellular properties of EPCs, adhesion, migration, and proliferation on fibronectin were significantly attenuated in IP-deficient EPCs compared with WT EPCs. In contrast, IP agonists facilitated these functions in WT EPCs, but not in IP-deficient EPCs. The specific deletion of IP in BM cells, which was performed by transplanting BM cells of IP-/- mice to WT mice, accelerated wire injury-mediated neointimal hyperplasia in the femoral artery. Notably, transfused WT EPCs, but not IP-deficient EPCs, were recruited to the injured vessels, participated in reendothelialization, and efficiently rescued the accelerated vascular remodeling.Conclusion-These findings clearly indicate that the prostaglandin I-2-IP system is essential for EPCs to accomplish their function and plays a critical role in the regulation of vascular remodeling. (Arterioscler Thromb Vasc Biol. 2010;30:464-470.)