Anagliptin inhibits neointimal hyperplasia after balloon injury via endothelial cell-specific modulation of SOD-1/RhoA/JNK signaling in the arterial wall
Anagliptin inhibits neointimal hyperplasia after balloon injury via endothelial cell-specific modulation of SOD-1/RhoA/JNK signaling in the arterial wall
复制标题
阿格列汀通过动脉壁内皮细胞特异性调节 SOD-1/RhoA/JNK 信号传导抑制球囊损伤后新生内膜增生
DOI：
10.1016/j.freeradbiomed.2018.04.580
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发表时间：
2018-06-01
影响因子：
7.4
通讯作者：
Chen, Chang
中科院分区：
文献类型：
--
作者：
Li, Qi;Zhang, Mingyu;Chen, Chang
内膜增生是支架植入术后的主要并发症之一，但其潜在机制尚不清楚。我们前期研究发现，二肽基肽酶IV （DPP-4）抑制剂阿格列汀可抑制球囊损伤后的内膜增生。本研究进一步研究了阿格列汀对球囊损伤后内皮细胞（EC）迁移的影响。结果显示，阿格列汀通过刺激内皮细胞的迁移显著减少了内膜增生，但对球囊损伤后的内侧区域没有影响。阿格列汀通过上调球囊损伤后血浆SOD-1水平而非SOD-2水平来提高血浆SOD总活性。同时，阿格列汀预孵育可抑制过氧化氢介导的HUVECs氧化物质的形成和细胞凋亡。Anagliptin体外预孵育通过SOD-1/RhoA/JNK信号通路介导Factin的形成，促进HUVECs的迁移。总的来说，DPP-4抑制剂Anagliptin调节SOD-1/RhoA/ jnk介导的HUVECs迁移。提示阿格列汀可作为预防球囊损伤后内膜增生的潜在药物。
Intimal hyperplasia is one of the major complications after stenting, but the underlying mechanisms remain unclear. Our previous study found that the dipeptidyl peptidase IV (DPP-4) inhibitor, Anagliptin, suppresses intimal hyperplasia after balloon injury. Here, we further investigated the effects of Anagliptin on endothelial cell (EC) migration after balloon injury. The results showed that Anagliptin administration significantly reduced intimal hyperplasia by stimulating the migration of endothelial cells, but had no effect on the medial area after balloon injury. Anagliptin elevated the total plasma activity of SOD by up-regulating the level of SOD-1, but not SOD-2, after balloon injury. Meanwhile, pre-incubation with Anagliptin suppressed the hydrogen peroxide-mediated formation of oxidant species and apoptosis in HUVECs. In vitro pre-incubation with Anagliptin promoted the migration of HUVECs via the SOD-1/RhoA/JNK signaling pathway mediating the formation of Factin. Collectively, the DPP-4 inhibitor, Anagliptin, regulates SOD-1/RhoA/JNK-mediated HUVECs migration. The results suggest that Anagliptin could serve as a potential drug to prevent intimal hyperplasia formation after balloon injury.