Department of Pharmacology, Asahikawa Medical College, Midorigaoka Higashi 2-1-1-1, Asahikawa 078-8510, Japan.
Arterioscler Thromb Vasc Biol. 2010 Mar;30(3):464-70. doi: 10.1161/ATVBAHA.109.193730. Epub 2009 Dec 10.
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.
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.
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.
内皮祖细胞（EPCs）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。我们评估了前列腺素 I（2）是否在调节 EPCs 的功能以限制血管重塑中发挥作用。
从野生型（WT）小鼠或缺乏前列腺素 I（2）受体 IP（IP（-/-）小鼠）的骨髓（BM）中分离 EPCs（Lin（-）cKit（+）Flk-1（+）细胞）。逆转录聚合酶链反应分析表明，BM 细胞中的 EPCs特异性表达 IP。与 WT EPCs 相比，IP 缺陷型 EPCs 的细胞特性、在纤维连接蛋白上的黏附、迁移和增殖明显减弱。相比之下，IP 激动剂促进了 WT EPCs 中的这些功能，但不能促进 IP 缺陷型 EPCs 中的这些功能。通过将 IP（-/-）小鼠的 BM 细胞移植到 WT 小鼠中，特异性地在 BM 细胞中缺失 IP，加速了股动脉中 wire 损伤介导的内膜增生。值得注意的是，转输的 WT EPCs，但不是 IP 缺陷型 EPCs，被募集到受损的血管中，参与再内皮化，并有效地挽救了加速的血管重塑。
这些发现清楚地表明，前列腺素 I（2）-IP 系统对于 EPCs 完成其功能是必不可少的，并且在调节血管重塑中起着关键作用。
