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Chemokine (C–X–C motif) receptor 2 blockade by SB265610 inhibited angiotensin II-induced abdominal aortic aneurysm in Apo E−/− mice

  • Hao Nie
  • Hong-Xia Wang
  • Cui Tian
  • Hua-Liang Ren
  • Fang-Da Li
  • Chao-Yu Wang
  • Hui-Hua Li
  • Yue-Hong Zheng
Original Article
  • 21 Downloads

Abstract

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.

Keywords

Chemoreceptor CXCR2 AAA Inflammation Macrophage 

Abbreviations

CXCR2

Chemokine (C–X–C motif) receptor 2

AAA

Abdominal aortic aneurysms

Ang II

Angiotensin II

MMPs

Metalloproteinases

DCs

Dendritic cells

TNF-α

Tumor necrosis factor-α

IFN-γ

Interferon-γ

Notes

Acknowledgements

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.

Supplementary material

380_2018_1301_MOESM1_ESM.docx (15 kb)
Supplementary material 1 (DOCX 15 kb)

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Copyright information

© Springer Japan KK, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Vascular SurgeryPeking Union Medical College HospitalBeijingPeople’s Republic of China
  2. 2.Department of Physiology and Pathophysiology, School of Basic Medical SciencesCapital Medical UniversityBeijingPeople’s Republic of China
  3. 3.Department of Cardiology, Institute of Cardiovascular DiseasesFirst Affiliated Hospital of Dalian Medical UniversityDalianPeople’s Republic of China

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