Related Experiment Video
Updated: Jul 18, 2026
Subcutaneous Angiotensin II Infusion using Osmotic Pumps Induces Aortic Aneurysms in Mice
Published on: September 28, 2015
Genetic deficiency of cyclooxygenase-2 attenuates abdominal aortic aneurysm formation in mice
Jonathan M Gitlin1, Darshini B Trivedi, Robert Langenbach
1Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0082, USA.
Objective:
Abdominal aortic aneurysms (AAAs) are characterized by chronic inflammation which contributes to the remodeling and eventual weakening of the vessel wall. Increased cyclooxygenase-2 (COX-2) expression is detected in human aneurysmal tissue and is suggested to contribute to the disease. The aim of the current study was to define the role of COX-2 expression in the development of AAAs, using a model of the disease.
Methods:
AAAs were induced in mice by chronic angiotensin II infusion, and were analyzed following 3, 7, 21 or 28 days of the infusion. AAA incidence and severity, together with the expression of inflammatory markers, were compared between abdominal aortas from COX-2-deficient mice and their wild-type littermate controls.
Results:
The AAA incidence in COX-2 wild-type mice was 54% (13/24), whereas AAAs were not detected in COX-2-deficient mice (0/23) following 28 days of angiotensin II infusion. The genetic deficiency of COX-2 also resulted in a 73% and 90% reduction in AAA incidence following 7 and 21 days of angiotensin II infusion, respectively. In COX-2 wild-type mice, COX-2 mRNA expression in the abdominal aorta was induced by angiotensin II beginning 3 days following initiation of the infusion, which continued throughout progression of the disease. Abundant COX-2 protein expression was detected in medial smooth muscle cells adjacent to the AAAs. The deficiency of COX-2 significantly attenuated mRNA expression in the abdominal aorta of the macrophage marker CD68, and the inflammatory cell recruitment chemokines, monocyte chemotactic protein-1 and macrophage inflammatory protein-1alpha.
Conclusions:
Our findings suggest that increased COX-2 expression in smooth muscle cells of the abdominal aorta contributes to AAA formation in mice by enhancing inflammatory cell infiltration.
Insights
Cyclooxygenase-2 (COX-2) deficiency prevents abdominal aortic aneurysm (AAA) formation in mice. Reduced COX-2 expression significantly lowers AAA incidence and inflammatory cell infiltration, highlighting COX-2
Area of Science:
- Vascular Biology
- Inflammation Research
- Atherosclerosis
Background:
- Abdominal aortic aneurysms (AAAs) involve chronic inflammation and vessel wall remodeling.
- Increased cyclooxygenase-2 (COX-2) expression is observed in human AAA tissue.
- The precise role of COX-2 in AAA development requires further elucidation.
Purpose of the Study:
- To investigate the role of COX-2 in the development of abdominal aortic aneurysms.
- To compare AAA formation in COX-2-deficient mice versus wild-type controls.
Main Methods:
- Abdominal aortic aneurysms were induced in mice using chronic angiotensin II infusion.
- AAA incidence and severity were assessed at multiple time points (3, 7, 21, 28 days).
- Expression of inflammatory markers was compared between COX-2-deficient and wild-type mice.
Main Results:
- AAA incidence was 54% in wild-type mice but 0% in COX-2-deficient mice after 28 days.
- COX-2 deficiency markedly reduced AAA incidence at 7 and 21 days (73% and 90% reduction, respectively).
- Angiotensin II induced COX-2 expression in wild-type aortas; COX-2 deficiency attenuated inflammatory markers like CD68, MCP-1, and MIP-1alpha.
Conclusions:
- Increased COX-2 expression in aortic smooth muscle cells promotes AAA formation.
- COX-2 contributes to AAA development by enhancing inflammatory cell infiltration.
- Targeting COX-2 may offer a therapeutic strategy for abdominal aortic aneurysms.
