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Stromal cell-derived factor-1 exerts opposing roles through CXCR4 and CXCR7 in angiotensin II-induced adventitial

Bei Song1, Dongrui Chen2, Zixiong Liu3

  • 1Department of Cardiovascular Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Department of General Practice, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Biochemical and Biophysical Research Communications
|January 23, 2022
PubMed

Insights

Stromal cell-derived factor-1 (SDF-1) has opposing roles in hypertension. Blocking SDF-1/CXCR4 worsens vascular remodeling, while blocking CXCR7 improves it, suggesting differential receptor involvement.

Area of Science:

  • Cardiovascular Biology
  • Molecular Medicine
  • Immunology

Background:

  • Hypertension involves vascular adventitia inflammation and immune responses.
  • Stromal cell-derived factor-1 (SDF-1) and its receptors CXCR4 and CXCR7 are implicated in tissue repair and tumor growth.
  • The role of the SDF-1/CXCR4/CXCR7 axis in hypertensive vascular remodeling remains unclear.

Purpose of the Study:

  • To investigate the involvement of the SDF-1/CXCR4/CXCR7 axis in angiotensin II (AngII)-induced hypertensive vascular remodeling.
  • To elucidate the distinct roles of CXCR4 and CXCR7 in mediating the effects of SDF-1 in the vascular adventitia.

Main Methods:

  • Utilized lentivirus-mediated shRNA to knockdown SDF-1 and CXCR7 in a mouse model of AngII-induced hypertension.
  • Administered CXCR4 antagonist AMD3100 and CXCR7 agonist VUF11207.
  • Examined effects on adventitial thickening, fibrosis, and collagen I deposition in vivo.
  • Assessed inflammation, proliferation, and migration in cultured adventitial fibroblasts (AFs) in vitro.

Main Results:

  • AngII infusion increased SDF-1 expression in the vascular adventitia.
  • Blockade of the SDF-1/CXCR4 axis exacerbated AngII-induced adventitial thickening and fibrosis.
  • CXCR7 knockdown attenuated adventitial remodeling, while CXCR7 activation potentiated it.
  • AMD3100 and VUF11207 aggravated AngII-induced inflammation, proliferation, and migration in cultured AFs.

Conclusions:

  • SDF-1 exerts opposing effects on AngII-induced vascular adventitial remodeling through its receptors CXCR4 and CXCR7.
  • CXCR4 blockade potentiates, while CXCR7 blockade attenuates, hypertensive vascular adventitial remodeling.
  • The SDF-1/CXCR4/CXCR7 axis represents a potential therapeutic target for hypertension-related vascular complications.

Keywords:
Adventitial remodelingAngiotensin IIC-X-C Motif chemokine receptor 4CXCR7HypertensionStromal cell-derived factor-1

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