Plerixafor stimulates adhesive activity and endothelial regeneration of endothelial progenitor cells via elevating CXCR7 expression

  • J Diabetes Complications. 2020 Oct;34(10):107654. doi: 10.1016/j.jdiacomp.2020.107654.
Chunyu Jiang  1 ,  Ruiting Li  1 ,  Xu Ma  1 ,  Hui Hu  1 ,  Liming Wei  1 ,  Jungong Zhao  2
Affiliations
  • 1. Department of Radiology, The Sixth People's Hospital, Affiliated to Shanghai Jiao Tong University, 600 Yi-Shan Road, Shanghai 200233, PR China.
  • 2. Department of Radiology, The Sixth People's Hospital, Affiliated to Shanghai Jiao Tong University, 600 Yi-Shan Road, Shanghai 200233, PR China.. Electronic address: [email protected].
PMID: 32741660 DOI: 10.1016/j.jdiacomp.2020.107654
Abstract

Aims: To assess the effects of plerixafor on function and endothelial regeneration of endothelial progenitor cells (EPCs).

Methods: The proliferation and adhesion capacity of EPCs were evaluated in vitro. Furthermore, the expression levels of CXC chemokine receptor-7 (CXCR7) were detected before and after treatment with plerixafor. The CXCR7 expression of EPCs was knocked-down by RNA interference to evaluate the role of CXCR7 in regulating function of EPCs. A rat carotid artery injury model was established to assess the influences of plerixafor on endothelial regeneration.

Results: Plerixafor stimulated adhesion capacity of EPCs, associating with upregulation of CXCR7 and activation of LFA-1 and VLA-4 molecules. Knockdown of CXCR7 slightly impaired proliferation capacity but significantly attenuated adhesion capacity of EPCs. Plerixafor facilitated endothelial repair at 7 days, while reduced neointimal hyperplasia at 7 and 14 days via recruiting more EPCs participating in endothelial reparation.

Conclusions: Plerixafor can positively regulate adhesion capacity of EPCs to HUVECs via elevating the expression level of CXCR7 and stimulating LFA-1 and VLA-4 molecules activation. Treatment with plerixafor accelerated re-endothelialization and inhibited neointimal hyperplasia after endoth elial injury, indicating that it can to be used for endothelial regeneration.

Keywords
CXCL12; CXCR7; Endothelial progenitor cells; Neointimal hyperplasia; Plerixafor.
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