Inhibition of CXCR2 alleviates the development of abdominal aortic aneurysm in Apo E-/- mice

Purpose: To investigate the relationship between atherosclerotic abdominal aortic aneurysm (AAA) and CXC chemokine receptor type 2 (CXCR2). Methods: Mouse AAA model was established by embedding angiotensin-II pump (1000 ng/kg/min) in ApoE(-/-) mice. Mice were received SB225002, a selective CXCR2 antagonist, for treatment. Blood pressure was recorded, and CXCR2(+) macrophages were examined by flow cytometry analysis. Terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) staining was performed to detect cell apoptosis of abdominal aortic aneurysms. Macrophages were isolated from ApoE(-/-) mice and treated with Ang II and/or SB225002. Dihydroethidium staining was carried out to determine reactive oxygen species (ROS) activity. Enzyme-linked immunosorbent assay (ELISA) was performed to determine the production of IL-1 beta and TNF-alpha. The corresponding gene expressions were measured using real-time polymerase chain reaction (PCR), western blot, and immunohistochemistry staining. Results: We found that Ang II activated the expression of CXCR2 in monocytes during the formation of AM. Inhibition of CXCR2 significantly reduced the size of AAA, attenuated inflammation and phenotypic changes in blood vessels. Ang II-induced macrophages exhibited elevated ROS activity, and elevated levels of IL-1 beta and TNF-alpha, which were then partly abolished by SB225002. Conclusion: CXCR2 plays an important role in AAA, suggesting that inhibiting CXCR2 may be a new treatment for AAA.

Automated summary

The study investigated the relationship between atherosclerotic abdominal aortic aneurysm (AAA) and CXC chemokine receptor type 2 (CXCR2) using a mouse model. Inhibition of CXCR2 was shown to reduce the size of AAA, inflammation, and phenotypic changes in blood vessels, suggesting that targeting CXCR2 may be a new treatment strategy for AAA.