The effect of quercetin on aortic aneurysms in mice

[Speaker] Yuki Izawa-Ishizawa:1
[Co-author] Masaki Imanishi:2, Kotoko Suzuki:3, Yuya Horinouchi:1, Kenshi Takechi:4, Yoshito Zamami:2,3, Koichiro Tsuchiya:5, Toshiaki Tamaki:1, Keisuke Ishizawa:2,3, Yasumasa Ikeda:1
1:Pharmacology, Tokushima University, Graduate School of Biomedical Sciences, Japan, 2:Pharmacy, Tokushima University Hospital, Japan, 3:Clinical Pharmacology and Therapeutics, Tokushima University, Graduate School of Biomedical Sciences, Japan, 4:Medical Pharmacology, Tokushima University, Graduate School of Biomedical Sciences, Japan, 5:Clinical Trial Center for Developmental Therapeutics, Tokushima University Hospital, Japan

Purpose: Aortic aneurysms (AAs) are common diseases among the elderly people and rupture of AAs carry a risk of death up to 90%. Even surgical intervention takes large risks of mortality. However, there is currently no management to prevent the formation of AAs. Quercetin is an abundant polyphenol in onions, fruits, and so on. It has been reported that quercetin is effective to improve vascular function. In this study, we investigated the effects of quercetin on pharmacologically-induced AAs in mice. Methods: In 10-week-old C57BL/6J male mice, hypertension was induced by angiotensin (Ang) II (1000 ng/kg/min) for 6 weeks. β-aminopropionitrile (BAPN) (150 mg/kg/day) was administered for the first 2 weeks by osmotic pump to induce degeneration of elastic lamina. Quercetin was administered orally at 60 mg/kg/day from 2 weeks prior to the start of Ang II and BAPN (AB) loading until the end of the examinations. The aortae were harvested at the day of death or at the end of the treatments. The onset of AAs was judged by the over 1.5 times enlargement of aortic diameter compared to the minimum diameter. Protein or mRNA samples from mice aortic tissues were subjected western blotting analysis, zymography assay, and real time PCR. Results: The AB loading induced degenerative aneurysm of the thoracic and/or abdominal aorta. Although there was no difference in systolic blood pressure (SBP) between the AB group and quercetin-treated group, quercetin treatment showed the reduction of the incidence of AAs and the death from aortic rupture. Quercetin significantly suppressed the enlargement of abdominal aortae and the degeneration of elastic lamina within the aortic wall observed under the Elastica van Gieson's staining. The activity of matrix metalloproteinase (MMP)-2/9 were upregulated in aortae from AB mice, but suppressed by quercetin treatment. The expressions of vascular endothelial cell adhesion molecule-1 and F4/80, a marker of macrophages, are also suppressed in quercetin treated group. Conclusions: These findings suggest that quercetin prevents aneurysm progression via its protective effects against elastin degeneration and inflammatory cell infiltration.
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