4.2 Article

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

Journal

HEART AND VESSELS
Volume 34, Issue 5, Pages 875-882

Publisher

SPRINGER
DOI: 10.1007/s00380-018-1301-7

Keywords

Chemoreceptor; CXCR2; AAA; Inflammation; Macrophage

Funding

  1. Natural Science Foundation of China [81770481]
  2. CAMS Innovation Fund for Medical Sciences (CIFMS) [2017-12M-1-008]

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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.

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