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

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.

• Authors: Hao Nie, Hong-Xia Wang, Cui Tian, Hua-Liang Ren, Fang-Da Li, Chao-Yu Wang, Hui-Hua Li, Yue-Hong Zheng
• Journal: Heart and vessels (Heart Vessels) Vol. 34 Issue 5 Pg. 875-882 (May 2019) ISSN: 1615-2573 [Electronic] Japan
• PMID: 30535755 (Publication Type: Journal Article)

Chemical References

• 1-(2-bromophenyl)-3-(7-cyano-3H-benzotriazol-4-yl)urea
• Phenylurea Compounds
• Receptors, Interleukin-8B
• Triazoles
• Angiotensin II

Topics

• Angiotensin II (adverse effects)
• Animals
• Aortic Aneurysm, Abdominal (chemically induced, drug therapy)
• Disease Models, Animal
• Humans
• Macrophages (metabolism, pathology)
• Male
• Mice
• Mice, Knockout, ApoE
• Phenylurea Compounds (pharmacology)
• Receptors, Interleukin-8B (antagonists & inhibitors)
• Signal Transduction
• Triazoles (pharmacology)