Glucagon-like peptide-1 inhibits the progression of abdominal aortic aneurysm in mice:The earlier the better

Abstract

Abstract ObjectivesGlucagon‑like peptide‑1 (GLP-1) has a cardiovascular-protective effect in preventing Abdominal Aortic Aneurysm (AAA) formation. However, the administration time to maximize the optimal effect has not been determined. We conducted this study to determine whether the GLP-1 receptor agonist, liraglutide, inhibited AAA progression of mice more efficiently during the earlier stages. Methods Mice were treated with 300ug/kg/day liraglutide 7, 14 and 28 days after aneurysm preparation. The morphology of abdominal aorta were followed up with 7.0 T magnetic resonance imaging (MRI) during the liraglutide administration. 28 days after administration, the AAA dilatation ratio calculation and histopathological examination were then conducted. Oxidative stress levels were evaluated by the expression of malondialdehyde (MDA). The inflammatory responses were also determined. Results Treatment with liraglutide decreased AAA formation. Specifically, expansion of the abdominal aorta, elastin lamina degradation and vascular inflammation by leukocyte infiltration decreased. Additionally, MDA expression and matrix metalloproteinase (MMP) activity reduced. Furthermore, the dilatation rate of aortic, MDA expression, leukocyte infiltration, and MMPs activity in the vascular wall decreased significantly in early stage. Conclusions GLP-1 treatment inhibited AAA progression in mice through its anti-inflammatory and anti-oxidant effects, especially during the earlier stages of AAA formation. Thus, GLP-1 may be a potential pharmacological target for AAA treatment.