Chemokine (C–X–C motif) receptor 2 blockade by SB265610 inhibited angiotensin II-induced abdominal aortic aneurysm in Apo E−/− mice
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Inflammation plays a critical role in the development of abdominal aortic aneurysm (AAA). Chemokine receptor CXCR2 mediates inflammatory cell chemotaxis in several diseases. However, the role of CXCR2 in AAA and the underlying mechanisms remain unknown. In this study, we found that the CXCR2 expressions in AAA tissues from human and angiotensin II (Ang II)-infused apolipoprotein E knockout (Apo E−/−) mice were significantly increased. The pharmacological inhibition of CXCR2 (SB265610) markedly reduced Ang II-induced AAA formation. Furthermore, SB265610 treatment significantly reduced collagen deposition, elastin degradation, the metal matrix metalloprotease expression and accumulation of macrophage cells. In conclusion, these results showed CXCR2 plays a pathogenic role in AAA formation. Inhibition of CXCR2 pathway may represent a novel therapeutic approach to treat AAA.
KeywordsChemoreceptor CXCR2 AAA Inflammation Macrophage
Chemokine (C–X–C motif) receptor 2
Abdominal aortic aneurysms
- Ang II
Tumor necrosis factor-α
We would like to acknowledge funding support from The Natural Science Foundation of China (81770481) and CAMS Innovation Fund for Medical Sciences (CIFMS, 2017-12M-1-008).
Compliance with ethical standards
Conflict of interest
The authors declare that there are no competing or financial interests associated with the manuscript.
- 7.Tarzami ST, Miao W, Mani K, Lopez L, Factor SM, Berman JW, Kitsis RN (2003) Opposing effects mediated by the chemokine receptor CXCR2 on myocardial ischemia-reperfusion injury: recruitment of potentially damaging neutrophils and direct myocardial protection. Circulation 108(19):2387–2392CrossRefPubMedGoogle Scholar
- 8.Coelho FM, Pinho V, Amaral FA, Sachs D, Costa VV, Rodrigues DH, Vieira AT, Silva TA, Souza DG, Bertini R, Teixeira AL, Teixeira MM (2008) The chemokine receptors CXCR1/CXCR2 modulate antigen-induced arthritis by regulating adhesion of neutrophils to the synovial microvasculature. Arthritis Rheum 58(8):2329–2337CrossRefPubMedGoogle Scholar
- 10.Wang L, Zhao XC, Cui W, Ma YQ, Ren HL, Zhou X, Fassett J, Yang YZ, Chen Y, Xia YL, Du J, Li HH (2016) Genetic and pharmacologic inhibition of the chemokine receptor CXCR2 prevents experimental hypertension and vascular dysfunction. Circulation 134(18):1353–1368CrossRefPubMedPubMedCentralGoogle Scholar
- 19.Long MY, Li HH, Pen XZ, Huang MQ, Luo DY, Wang PS (2014) Expression of chemokine receptor-4 in bone marrow mesenchymal stem cells on experimental rat abdominal aortic aneurysms and the migration of bone marrow mesenchymal stem cells with stromal-derived factor-1. Kaohsiung J Med Sci 30(5):224–228CrossRefPubMedGoogle Scholar
- 22.Wang J, Lindholt JS, Sukhova GK, Shi MA, Xia M, Chen H, Xiang M, He A, Wang Y, Xiong N, Libby P, Wang JA, Shi GP (2014) IgE actions on CD4+ T cells, mast cells, and macrophages participate in the pathogenesis of experimental abdominal aortic aneurysms. EMBO Mol Med 6(7):952–969CrossRefPubMedPubMedCentralGoogle Scholar