Department of Radiology, The Sixth People's Hospital, Affiliated to Shanghai Jiao Tong University, Shanghai 200233, P.R. China.
Department of Hematology, The Sixth People's Hospital, Affiliated to Shanghai Jiao Tong University, Shanghai 200233, P.R. China.
Mol Med Rep. 2020 Oct;22(4):3201-3212. doi: 10.3892/mmr.2020.11432. Epub 2020 Aug 13.
The present study was conducted to assess the effects of AMD3100 and stromal cell-derived factor 1 (SDF-1) on cellular functions and endothelial regeneration of endothelial progenitor cells (EPCs). The cell proliferation and adhesion capacity of EPCs were evaluated in vitro following treatment with AMD3100 and SDF‑1 using a Cell Counting Kit‑8 assay. Furthermore, the expression levels of C‑X‑C motif chemokine receptor 4 (CXCR4) and C‑X‑C motif chemokine receptor 7 (CXCR7) were detected before and after treatment with AMD3100 and SDF‑1 to elucidate their possible role in regulating the cellular function of EPCs. A rat carotid artery injury model was established to assess the influences of AMD3100 and SDF‑1 on endothelial regeneration. AMD3100 reduced the proliferation and adhesion capacity of EPCs to fibronectin (FN), whereas it increased the adhesion capacity of EPCs to human umbilical vein endothelial cells (HUVECs). However, SDF‑1 stimulated the proliferation and cell adhesion capacity of EPCs to HUVECs and FN. Additionally, the expression levels of CXCR7 but not CXCR4 were upregulated following AMD3100 treatment, whereas the expression levels of both CXCR4 and CXCR7 were upregulated after SDF‑1 treatment. In vivo results demonstrated that AMD3100 increased the number of EPCs in the peripheral blood and facilitated endothelial repair at 7 days after treatment. However, local administration of SDF‑1 alone did not enhance reendothelialization 7 and 14 days after treatment. Importantly, the combination of AMD3100 with SDF‑1 exhibited superior therapeutic effects compared with AMD3100 treatment alone, accelerated reendothelialization 7 days after treatment, and attenuated neointimal hyperplasia at day 7 and 14 by recruiting more EPCs to the injury site. In conclusion, AMD3100 could positively regulate the adhesion capacity of EPCs to HUVECs via elevation of the expression levels of CXCR7 but not CXCR4, whereas SDF‑1 could stimulate the proliferation and adhesion capacity of EPCs to FN and HUVECs by elevating the expression levels of CXCR4 and CXCR7. AMD3100 combined with SDF‑1 outperformed AMD3100 alone, promoted early reendothelialization and inhibited neointimal hyperplasia, indicating that early reendothelialization attenuated neointimal hypoplasia following endothelial injury.
本研究旨在评估 AMD3100 和基质细胞衍生因子 1（SDF-1）对内皮祖细胞（EPC）的细胞功能和内皮再生的影响。采用细胞计数试剂盒-8 检测法，检测 AMD3100 和 SDF-1 处理后 EPC 的细胞增殖和黏附能力。此外，在 AMD3100 和 SDF-1 处理前后检测 C-X-C 基序趋化因子受体 4（CXCR4）和 C-X-C 基序趋化因子受体 7（CXCR7）的表达水平，以阐明它们在调节 EPC 细胞功能中的可能作用。建立大鼠颈动脉损伤模型，评估 AMD3100 和 SDF-1 对内皮再生的影响。AMD3100 降低 EPC 对纤维连接蛋白（FN）的增殖和黏附能力，而增加 EPC 与人脐静脉内皮细胞（HUVEC）的黏附能力。然而，SDF-1 刺激 EPC 对 HUVEC 和 FN 的增殖和细胞黏附能力。此外，AMD3100 处理后 CXCR7 的表达水平上调，但 CXCR4 的表达水平不变，而 SDF-1 处理后 CXCR4 和 CXCR7 的表达水平均上调。体内结果表明，AMD3100 增加外周血中 EPC 的数量，并在治疗后 7 天促进内皮修复。然而，局部给予 SDF-1 本身并不能增强治疗后 7 天和 14 天的再内皮化。重要的是，AMD3100 与 SDF-1 联合应用的治疗效果优于 AMD3100 单独应用，加速了治疗后 7 天的再内皮化，并通过募集更多的 EPC 到损伤部位，减轻了第 7 天和第 14 天的新生内膜增生。总之，AMD3100 可通过上调 CXCR7 的表达水平而不是 CXCR4 的表达水平来正向调节 EPC 对 HUVEC 的黏附能力，而 SDF-1 则通过上调 CXCR4 和 CXCR7 的表达水平来刺激 EPC 对 FN 和 HUVEC 的增殖和黏附能力。AMD3100 联合 SDF-1 的效果优于 AMD3100 单独应用，促进早期再内皮化并抑制新生内膜增生，表明内皮损伤后早期再内皮化可减轻新生内膜萎缩。
