1. Stromal cell-derived factor-1 exerts opposing roles through CXCR4 and CXCR7 in angiotensin II-induced adventitial remodeling.
- Author
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Song, Bei, Chen, Dongrui, Liu, Zixiong, Cheng, Yuwen, Zhang, Zebei, Han, Weiqing, Zhang, Ruiyan, and Gong, Yanchun
- Subjects
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CXCR4 receptors , *CHEMOKINE receptors , *ANGIOTENSINS , *ANGIOTENSIN II , *VASCULAR remodeling , *TUMOR growth , *STROMAL cell-derived factor 1 - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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