Cysteine Leukotriene Receptor Antagonist—Montelukast—Treatment Improves Experimental Abdominal Aortic Aneurysms in Mice

Abstract

Background: Cysteinyl leukotrienes (LTs) and their receptors are involved in the pathogenesis of abdominal aortic aneurysms (AAAs). However, whether CysLT1 receptor antagonists such as montelukast can influence experimental nondissecting AAA remains unclear.

Methods: Nondissecting AAAs were induced in C57BL/6J mice by transient aortic luminal infusion of porcine pancreatic elastase (PPE). All animals were administrated montelukast (1 or 10 mg/kg, daily) or vehicle by gavage beginning 1 day before PPE infusion for 14 days. On day 0 (baseline) and day 14 after PPE infusion, abdominal aortic diameters were directly measured. Aortic aneurysmal segment samples were collected, and histopathological analysis was performed.

Results: Compared to vehicle treatment, montelukast significantly decreased PPE infusion–induced aortic expansion in a dose-dependent manner (0.09-mm reduction at a low dose and 0.19-mm reduction at a high dose). Histopathological analysis also revealed that compared with vehicle treatment, montelukast treatment, especially in the high-dose group, significantly improved PPE-induced aortic elastin degradation and medial smooth muscle cell depletion. Both doses of montelukast also markedly decreased the number of local leucocytes, including macrophages, CD4⁺ T cells, CD8⁺ T cells, and B cells, infiltration and accumulation in aortic aneurysmal lesions. Montelukast treatment also downregulated matrix metalloproteinase 2 (MMP2) and MMP9 expression and inhibited mural angiogenesis in aneurysmal aortas.

Conclusion: Montelukast treatment improves experimental nondissected AAAs in mice partly by improving aortic inflammation.