Preventive Effects of Quercetin against the Onset of Atherosclerosis-Related Acute Aortic Syndromes in Mice.

Mitsuhiro Goda,Yoshito Zamami,Kenta Yagi,Kenshi Takechi,Masayuki Chuma,Masateru Kondo,Koichi Tsuneyama,Yuu Kagimoto,Naoko Saito,Rie Matsuoka,Mayuko Hosooka,Yuki Izawa-Ishizawa,Keisuke Ishizawa

doi:10.3390/ijms21197226

Abstract

Atherosclerosis-related acute aortic syndromes, such as aortic aneurysms or aortic dissection are life-threatening diseases. Since they develop suddenly and progress rapidly, the establishment of preventive strategies is urgently needed. Quercetin, a flavonoid abundant in various vegetables and fruits, is suggested to reduce the risk of cardiovascular disease. Therefore, in this study, the preventive effect of quercetin was evaluated using a mouse model of aortic aneurysm and dissection. The model was established by administering angiotensin II (Ang II) and β-aminopropionitrile (BAPN), a lysyl oxidase inhibitor, to mice to induce hypertension and degeneration of the elastic lamina, which would eventually result in the onset of an aortic aneurysm. Ang II, BAPN, and a nitric oxide synthase inhibitor was administered to induce aortic dissection via endothelial dysfunction. Quercetin (60 mg/kg/day) was administered 2 weeks before inducing aortic diseases by the end of the experiments (8 weeks in the aneurysm model, 6 weeks in the dissection model). It was found to reduce the incidence of aneurysm (from 72 to 45%), dissection (from 17 to 10%), and rupture (from 33 to 15%) in mice. Elastin degradation was ameliorated in the quercetin-treated mice compared to that in the mice without quercetin treatment (degradation score 2.9 ± 0.3 vs 2.2 ± 0.2). Furthermore, quercetin suppressed the expression of vascular cell adhesion molecule-1, macrophage infiltration, and pro-matrix metalloproteinase-9 activity. Our results suggest that quercetin might prevent the onset of atherosclerosis-related acute aortic syndromes through its anti-inflammatory and endothelial cell-protective effects.

Highlights

Aortic aneurysms and aortic dissection are among the atherosclerosis-related acute aortic syndromes [1,2,3]
We examined the preventive effects of quercetin, for in vivo experiments, or Q3GA, for in vitro experiments, on the onset of aortic aneurysm or dissection
The preventive effects of quercetin against aortic aneurysm or dissection were examined using two different mouse models, which were designated as AB, by taking the acronym of two administered drugs; angiotensin II (Ang II) + β-aminopropionitrile (BAPN)-treated aortic aneurysm model mice, and LAB, by taking the acronym of three administered drugs; Nω-nitro-l-arginine methyl ester (l-NAME) + Ang II + BAPN-treated aortic dissection model mice

Summary

Introduction

Aortic aneurysms and aortic dissection are among the atherosclerosis-related acute aortic syndromes [1,2,3]. An aneurysm is a condition in which a part of the wall of the aorta circumferentially or locally enlarges or protrudes [4]. The known causes of aortic aneurysms are atherosclerosis, hypertension, and weakening of elastic lamina. An ultrasonic screening study revealed the prevalence of abdominal aortic aneurysms among individuals aged 65 years and higher is 4–7% in men and 1–2% in women [5]. Patients are asymptomatic initially but have a fatal outcome once the aneurysm ruptures [4]. Only antihypertensive agents have been used therapeutically against aortic aneurysm enlargement or aortic rupture [4]

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Conclusion