Abstract | BACKGROUND: The recruitment of leukocytes to the vascular wall is a key step in hypertension development. Chemokine receptor CXCR2 mediates inflammatory cell chemotaxis in several diseases. However, the role of CXCR2 in hypertension development and the underlying mechanisms remain unknown. METHODS: RESULTS:
Angiotensin II significantly upregulated the expression of CXCR2 mRNA and protein and increased the number of CD45+ CXCR2+ cells in mouse aorta (n=8 per group). Selective CXCR2 knockout (CXCR2-/-) or pharmacological inhibition of CXCR2 markedly reduced angiotensin II- or DOCA- salt-induced blood pressure elevation, aortic thickness and collagen deposition, accumulation of proinflammatory cells into the vascular wall, and expression of cytokines (n=8 per group). CXCR2 inhibition also ameliorated angiotensin II-induced vascular dysfunction and reduced vascular superoxide formation, NADPH activity, and expression of NADPH oxidase subunits (n=6 per group). Bone marrow reconstitution of wild-type mice with CXCR2-/- bone marrow cells also significantly abolished angiotensin II-induced responses (n=6 per group). It is important to note that CXCR2 blockade reversed established hypertension induced by angiotensin II or DOCA- salt challenge (n=10 per group). Furthermore, we demonstrated that CXCR2+ proinflammatory cells were higher in hypertensive patients ( n=30) compared with normotensive individuals (n=20). CONCLUSIONS: Infiltration of CXCR2+ cells plays a pathogenic role in arterial hypertension and vascular dysfunction. Inhibition of CXCR2 pathway may represent a novel therapeutic approach to treat hypertension.
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Authors | Lei Wang, Xue-Chen Zhao, Wei Cui, Yong-Qiang Ma, Hua-Liang Ren, Xin Zhou, John Fassett, Yan-Zong Yang, Yingjie Chen, Yun-Long Xia, Jie Du, Hui-Hua Li |
Journal | Circulation
(Circulation)
Vol. 134
Issue 18
Pg. 1353-1368
(Nov 01 2016)
ISSN: 1524-4539 [Electronic] United States |
PMID | 27678262
(Publication Type: Journal Article)
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Copyright | © 2016 The Authors. |
Chemical References |
- Receptors, Interleukin-8B
- Angiotensin II
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Topics |
- Angiotensin II
(pharmacology)
- Animals
- Disease Models, Animal
- Hypertension
(genetics, metabolism, prevention & control)
- Male
- Mice
- Mice, Knockout
- Receptors, Interleukin-8B
(antagonists & inhibitors, biosynthesis, genetics)
- Up-Regulation
(drug effects, genetics)
- Vascular Remodeling
(drug effects, genetics)
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