Glucagon-Like Peptide-1 Inhibits the Progression of Abdominal Aortic Aneurysm in Mice: The Earlier, the Better.

Abstract

Objectives: Glucagon-like peptide-1 (GLP-1) has a cardiovascular protective effect by preventing abdominal aortic aneurysm (AAA) formation. However, it is unclear at what point the agent should be administered to achieve the optimal effect. In this study, we aimed to determine whether administering the GLP-1 receptor agonist liraglutide during the earlier stages would more efficiently inhibit AAA progression in mice.

Methods: Depending on the group, mice were given a daily dose of 300 μg/kg liraglutide for 28 days at 7, 14, and 28 days after aneurysm induction. The morphology of the abdominal aorta was monitored using 7.0 T magnetic resonance imaging (MRI) during the administration of liraglutide. After 28 days of administration, the AAA dilatation ratio was calculated, and histopathological examination was performed. Oxidative stress levels were evaluated by the expression of malondialdehyde (MDA) and matrix metalloproteinases (MMPs). The inflammatory response was also evaluated.

Results: Liraglutide treatment led to a decrease in AAA formation, including a reduction in abdominal aorta expansion, elastin degradation in the elastic laminae, and vascular inflammation caused by leukocyte infiltration. The expression of MDA and the activity of MMPs (MMP-2, MMP-9) also decreased. Notably, administering liraglutide during the early stages resulted in a significant reduction in the dilatation rate of the aortic wall, as well as in MDA expression, leukocyte infiltration, and MMP activity in the vascular wall.

Conclusions: The GLP-1 receptor agonist liraglutide was found to inhibit AAA progression in mice by exerting anti-inflammatory and antioxidant effects, particularly during the early stages of AAA formation. Therefore, liraglutide may represent a potential pharmacological target for the treatment of AAA.