Xiang Yuan, Zhou Zhengshi, Zhu Lingping, Li Chuanchang, Luo Ying, Zhou Jipeng
Department of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Department of Laboratory Animal, Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, China.
Life Sci. 2023 Oct 15;331:122061. doi: 10.1016/j.lfs.2023.122061. Epub 2023 Aug 29.
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 × 10 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.
内皮祖细胞（EPCs）在血管修复中起重要作用。然而，在再狭窄过程中的炎症微环境中它们功能失调。在本研究中，我们调查了抗炎因子网膜素-1是否能通过改善因炎症而受损的EPC功能及其潜在机制，来减少大鼠颈动脉损伤（CAI）后的新生内膜形成。
用表达人网膜素-1或绿色荧光蛋白（GFP）的腺病毒载体转染EPCs。然后，大鼠在CAI后立即通过尾静脉注射接受2×10个表达网膜素-1或GFP的EPCs，并在24小时后再次注射。苏木精-伊红染色和免疫组织化学用于分析新生内膜增生。此外，用网膜素-1和肿瘤坏死因子-α（TNF-α）处理EPCs以研究潜在机制。
我们的结果表明，网膜素-1能显著改善EPC功能，包括增殖、凋亡和管腔形成。同时，过表达网膜素-1的EPCs能显著减少大鼠CAI后的新生内膜增生和肿瘤坏死因子-α（TNF-α）表达。TNF-α能显著诱导EPC功能障碍，而网膜素-1可通过抑制p38丝裂原活化蛋白激酶/环磷腺苷反应元件结合蛋白（p38 MAPK/CREB）途径显著逆转这种功能障碍。此外，p38 MAPK激动剂（茴香霉素）显著消除了网膜素-1对TNF-α损伤的EPCs的保护作用。
我们的结果表明，用网膜素-1对EPC进行基因改造可能是治疗再狭窄的一种替代策略。
