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Updated: Nov 16, 2025
Subcutaneous Angiotensin II Infusion using Osmotic Pumps Induces Aortic Aneurysms in Mice
Published on: September 28, 2015
Inhibition of CXCR2 alleviates the development of abdominal aortic aneurysm in Apo E-/- mice
Bo Sun1,2, Fangda Li3, Song Lai4
1Master. Chinese Academy of Medical Sciences - Peking Union Medical College Hospital - Department of Vascular Surgery - Beijing, China.
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-1β and TNF-α. 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 AAA. 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 1β and TNF-α, which were then partly abolished by SB225002.
Conclusions:
CXCR2 plays an important role in AAA, suggesting that inhibiting CXCR2 may be a new treatment for AAA.
Insights
CXC chemokine receptor type 2 (CXCR2) is crucial in abdominal aortic aneurysm (AAA) development. Inhibiting CXCR2 significantly reduced AAA size and inflammation, indicating its potential as a therapeutic target.
Area of Science:
- Cardiovascular Biology
- Immunology
- Vascular Biology
Background:
- Abdominal aortic aneurysm (AAA) is a life-threatening condition characterized by aortic wall weakening and dilation.
- The role of specific chemokine receptors, like CXC chemokine receptor type 2 (CXCR2), in AAA pathogenesis remains incompletely understood.
Purpose of the Study:
- To investigate the relationship between atherosclerotic abdominal aortic aneurysm (AAA) and CXC chemokine receptor type 2 (CXCR2).
- To evaluate the therapeutic potential of CXCR2 inhibition in a mouse model of AAA.
Main Methods:
- A mouse model of AAA was induced using angiotensin-II infusion in ApoE-/- mice.
- Mice were treated with SB225002, a selective CXCR2 antagonist.
- Flow cytometry, TUNEL staining, dihydroethidium staining, ELISA, real-time PCR, western blot, and immunohistochemistry were used to assess AAA progression, inflammation, apoptosis, ROS activity, and cytokine production.
Main Results:
- Angiotensin-II administration activated CXCR2 expression in monocytes during AAA formation.
- CXCR2 inhibition significantly reduced AAA size, attenuated vascular inflammation, and decreased phenotypic changes.
- SB225002 treatment partly abolished elevated reactive oxygen species (ROS) activity and levels of IL-1β and TNF-α in Ang II-induced macrophages.
Conclusions:
- CXCR2 plays a significant role in the development and progression of atherosclerotic abdominal aortic aneurysm.
- Inhibiting CXCR2 presents a promising novel therapeutic strategy for AAA treatment.
