Aged Garlic Extract Attenuates CaCl2-Induced Abdominal Aortic Aneurysm Formation by Inhibiting Matrix Metalloproteinase 9 Expression in Macrophages

Abstract

Abdominal aortic aneurysm (AAA) is a local enlargement of the abdominal aorta with the risk of its fatal rupture. With lack of established medical treatments reducing the AAA growth, the development of treatment strategies for AAA is warranted. In this study, we examined whether aged garlic extract (AGE), which reportedly has vasoprotective effects, attenuates AAA formation in an animal model. AAAs were induced via CaCl₂ application to the abdominal aortas of C57BL/6J mice. The intake of an AGE-containing diet attenuated the aortic dilatation after AAA induction. Histological analysis showed that the degradation of elastic fibers in AAAs was mild in mice fed AGE compared to that in control mice. In addition, the expression of matrix metalloproteinase 9 (MMP9), a proteolytic enzyme degrading aortic tissue, was decreased in AAAs from mice fed with AGE. In cultured macrophages, AGE significantly inhibited tumor necrosis factor (TNF)-α-induced Mmp9 mRNA expression. Furthermore, AGE attenuated TNF-α-induced extracellular signal-regulated kinase (ERK) phosphorylation and c-fos mRNA expression, suggesting the suppressive effect of AGE on ERK-c-Fos-MMP9 axis induced by TNF-α. The present findings indicate that AGE diminishes AAA formation by mitigating tissue destruction, highlighting the potential cardiovascular benefits of AGE intake.