Department of Interventional therapy, Beijing Anzhen Hospital, Capital Medical University, No. 2 Anzhen Road, Beijing, China.
Department of Radiology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, 610041, People's Republic of China.
Cardiovasc Drugs Ther. 2024 Oct;38(5):873-884. doi: 10.1007/s10557-023-07456-x. Epub 2023 May 5.
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.
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.
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.
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.
胰高血糖素样肽-1（GLP-1）通过防止腹主动脉瘤（AAA）形成具有心血管保护作用。然而，尚不清楚何时给予该药物才能达到最佳效果。在这项研究中，我们旨在确定在早期阶段给予 GLP-1 受体激动剂利拉鲁肽是否会更有效地抑制小鼠 AAA 的进展。
根据组别，在诱导 AAA 后第 7、14 和 28 天，每天给予小鼠 300μg/kg 的利拉鲁肽，持续 28 天。在给予利拉鲁肽期间，使用 7.0 T 磁共振成像（MRI）监测腹主动脉的形态。给药 28 天后，计算 AAA 扩张率，并进行组织病理学检查。通过丙二醛（MDA）和基质金属蛋白酶（MMPs）的表达评估氧化应激水平。还评估了炎症反应。
利拉鲁肽治疗导致 AAA 形成减少，包括腹主动脉扩张减少、弹性层中弹性蛋白降解以及白细胞浸润引起的血管炎症。MDA 的表达和 MMPs（MMP-2、MMP-9）的活性也降低。值得注意的是，在早期阶段给予利拉鲁肽可显著降低主动脉壁的扩张率，以及 MDA 表达、白细胞浸润和血管壁中 MMP 活性。
GLP-1 受体激动剂利拉鲁肽通过发挥抗炎和抗氧化作用抑制小鼠 AAA 的进展，特别是在 AAA 形成的早期阶段。因此，利拉鲁肽可能成为 AAA 治疗的潜在药物靶点。
