AMD3100 and SDF‑1 regulate cellular functions of endothelial progenitor cells and accelerate endothelial regeneration in a rat carotid artery injury model

Jiang,Chunyu; Li,Ruiting; Ma,Xu; Hu,Hui; Guo,Juan; Zhao,Jungong

doi:10.3892/mmr.2020.11432

AMD3100 and SDF‑1 regulate cellular functions of endothelial progenitor cells and accelerate endothelial regeneration in a rat carotid artery injury model

Authors:
- Chunyu Jiang
- Ruiting Li
- Xu Ma
- Hui Hu
- Juan Guo
- Jungong Zhao
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Affiliations: 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
Published online on: August 13, 2020 https://doi.org/10.3892/mmr.2020.11432
Pages: 3201-3212
Copyright: © Jiang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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