内皮祖细胞（EPCs）在血管修复中起着重要作用。然而，在再狭窄的炎症微环境中，它们的功能受损。在这项研究中，我们调查了一个抗炎因子奥曼汀-1是否能通过改善被炎症损伤的EPC功能和相关机制来减少大鼠颈动脉损伤（CAI）后内膜再生组织形成。我们将人奥曼汀-1或绿色荧光蛋白（GFP）转染的腺病毒载体注入到EPC中，并通过尾静脉注射的方式分两次直接给予大鼠2 × 106表达奥曼汀-1或GFP的EPC，最初损伤后和24小时后。我们使用苏木精伊红染色和免疫组织化学方法分析内膜增生。此外，我们用奥曼汀-1和TNF-α处理EPC以研究相关机制。结果显示，奥曼汀-1可以显著改善EPC的增殖、凋亡和管形成功能。同时，过表达奥曼汀-1的EPC可以显著减少大鼠CAI后的内膜增生和肿瘤坏死因子-α（TNF-α）表达。TNF-α可以显著诱导EPC功能障碍，而奥曼汀-1可以通过抑制p38 MAPK/CREB途径来显著逆转其功能障碍。此外，p38 MAPK激动剂（阿西莫林）显著削弱了奥曼汀-1在被TNF-α损伤的EPC上的保护作用。我们的结果表明，通过遗传修饰EPC来表达奥曼汀-1可能是治疗再狭窄的一种替代策略。opyright © 2023. Elsevier Inc.发布。

Endothelial progenitor cells (EPCs) play an important role in vascular repair. However, they are dysfunctional in the inflammatory microenvironment during restenosis. In this study, we investigated whether omentin-1, an anti-inflammatory factor, could reduce neointima formation after carotid artery injury (CAI) in rats by improving EPC functions that were damaged by inflammation and the underlying mechanisms.EPCs were transfected with adenoviral vectors expressing human omentin-1 or green fluorescent protein (GFP). Then, the rats received 2 × 106 EPCs expressing omentin-1 or GFP by tail vein injection directly after CAI and again 24 h later. Hematoxylin-eosin staining and immunohistochemistry were used for analyzing neointimal hyperplasia. Besides, EPCs were treated with omentin-1 and TNF-α to examine the underlying mechanism.Our results showed that omentin-1 could significantly improve EPC functions, including proliferation, apoptosis and tube formation. Meanwhile, EPCs overexpressed with omentin-1 could significantly reduce neointimal hyperplasia and tumor necrosis factor-α (TNF-α) expression after CAI in rats. TNF-α could notably induce EPC dysfunction, which could be markedly reversed by omentin-1 through the inhibition of the p38 MAPK/CREB pathway. Furthermore, a p38 MAPK agonist (anisomycin) significantly abrogated the protective effects of omentin-1 on EPCs damaged by TNF-α.Our results indicated that genetically modifying EPC with omentin-1 could be an alternative strategy for the treatment of restenosis.Copyright © 2023. Published by Elsevier Inc.