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Updated: May 23, 2026
Subcutaneous Angiotensin II Infusion using Osmotic Pumps Induces Aortic Aneurysms in Mice
Published on: September 28, 2015
Interleukin-5 is a potential mediator of angiotensin II-induced aneurysm formation in apolipoprotein E knockout mice
Jun Xu1, Brittney Ehrman, Linda M Graham
1Department of Vascular Surgery, Cleveland Clinic Lerner College of Medicine-CWRU, Cleveland, Ohio 44195, USA.
Background:
The aim of this study was to evaluate alterations in Th1 and Th2 cytokines during experimental abdominal aortic aneurysm (AAA) formation.
Methods:
AAAs were induced in apolipoprotein E null mice by infusing angiotensin II (Ang II, 1000 ng/kg/min). Aortic homogenates were assessed at 0, 7, 14, and 28 d (n = 11/time point) for select Th1 and Th2 cytokines by ELISA. Additional mice had co-administration of anti-IgG (n = 20) or anti-IL-5 (n = 20) and were assessed at 28 d for AAA. Aortic homogenates were assessed for MMP-2 and MMP-9 expression. Mouse aortic SMC (MASMC) and peritoneal-derived macrophages were treated with IL-5 (0-40 ng/mL), and cell extracts and media (0-48 h) were assessed for MMP-2 and MMP-9 expression.
Results:
Ang II infusion was associated with a 3.4-fold (P < 0.01) and 3.6-fold (P < 0.01) increase in IL-5 and IL-10 (respectively), and a 0.6-fold reduction in IL-6, by 7 d. Anti-IL-5, but not anti-IgG, ameliorated Ang II-induced AAA formation. Up-regulation of MMP-2 and MMP-9 was observed in aneurysmal aortas, but not in the aortas obtained from mice treated with anti-IL-5. IL-5 stimulation of MASMC increased MMP-2 and MMP-9 mRNA (2.1-fold and 2.7-fold, respectively, P < 0.01) and protein (1.6-fold and 1.9-fold, respectively, P < 0.01) by 24 h. IL-5 stimulation of macrophages did not alter MMP expression.
Conclusions:
Ang II induces increased Th2 cytokines IL-5 and IL-10 early in the course of experimental AAA formation, and inhibition of IL-5 prevents AAA formation suggesting an important role. While IL-5 is capable of up-regulating MMP-2 and MMP-9 expression in MASMC, investigations into alternate roles in AAA formation is warranted.
