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

• Published in: Biochemical and biophysical research communications 2022-02, Vol.594, p.38-45
• Main Authors: Song, Bei, Chen, Dongrui, Liu, Zixiong, Cheng, Yuwen, Zhang, Zebei, Han, Weiqing, Zhang, Ruiyan, Gong, Yanchun
• Format: Article
• Language: English
• Subjects: Adventitia - metabolism; Adventitial remodeling; Angiotensin II; Angiotensin II - metabolism; Animals; Benzylamines - pharmacology; C-X-C Motif chemokine receptor 4; Cell Movement - physiology; Cell Proliferation; Chemokine CXCL12 - metabolism; Collagen - metabolism; CXCR7; Cyclams - pharmacology; Disease Models, Animal; Fibroblasts - pathology; Fibrosis; Hypertension; Hypertension - metabolism; Male; Mice; Mice, Inbred C57BL; Rats; Rats, Sprague-Dawley; Receptors, CXCR - metabolism; Receptors, CXCR4 - metabolism; Signal Transduction; Stromal cell-derived factor-1; Wound Healing
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2022.01.030

Recent studies have emphasized the role of vascular adventitia inflammation and immune response in hypertension. It has been reported that stromal cell-derived factor-1 (SDF-1) plays various biological functions through its receptors C-X-C motif chemokine receptor 4 (CXCR4) and CXCR7 in tumor growth and tissue repair. However, it is unclear that whether SDF-1/CXCR4/CXCR7 axis is involved in hypertensive vascular remodeling. In the present study, the involvement of SDF-1/CXCR4/CXCR7 axis was evaluated with lentivirus-mediated shRNA of SDF-1 and CXCR7, CXCR4 antagonist AMD3100 and CXCR7 agonist VUF11207 in angiotensin II (AngII)-induced hypertensive mice and in cultured adventitial fibroblasts (AFs). Results showed that AngII infusion markedly increased SDF-1 expressed in vascular adventitia, but not in media and endothelium. Importantly, blockade of SDF-1/CXCR4 axis strikingly potentiated AngII-induced adventitial thickening and fibrosis, as indicated by enhanced collagen I deposition. In contrast, CXCR7 shRNA largely attenuated AngII-induced adventitial thickness and fibrosis, whereas CXCR7 activation with VUF11207 significantly potentiated AngII-induced adventitial thickening and fibrosis. In consistent with these in vivo study, CXCR4 inhibition with AMD3100 and CXCR7 activation with VUF11207 aggravated AngII-induced inflammation, proliferation and migration in cultured AFs. In summary, these results suggested that SDF-1 exerted opposing effects through CXCR4 and CXCR7 in AngII-induced vascular adventitial remodeling. •AngII infusion results in marked increase of SDF-1 levels in thoracic adventitia, but not in media and endothelium.•Blocking SDF-1/CXCR4 axis promotes thoracic adventitial thickening and fibrosis in AngII-induced hypertensive mice。.•CXCR7 plays a detrimental role in AngII-induced thoracic adventitial thickening and fibrosis.