Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences, Tokushima 770-8503, Japan.
Department of Pharmacy, Tokushima University Hospital, Tokushima 770-8503, Japan.
Int J Mol Sci. 2020 Sep 30;21(19):7226. doi: 10.3390/ijms21197226.
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.
动脉粥样硬化相关的急性主动脉综合征,如主动脉瘤或主动脉夹层,是危及生命的疾病。由于它们突然发生并迅速进展,因此迫切需要建立预防策略。槲皮素是一种在各种蔬菜和水果中含量丰富的类黄酮,据推测它可以降低心血管疾病的风险。因此,在这项研究中,使用主动脉瘤和夹层的小鼠模型评估了槲皮素的预防作用。该模型通过给予血管紧张素 II(Ang II)和β-氨基丙腈(BAPN)(一种赖氨酰氧化酶抑制剂)来建立,以诱导高血压和弹性膜的退化,最终导致主动脉瘤的发生。通过内皮功能障碍给予 Ang II、BAPN 和一氧化氮合酶抑制剂来诱导主动脉夹层。在通过实验结束时(动脉瘤模型为 8 周,夹层模型为 6 周)诱发主动脉疾病之前 2 周给予槲皮素(60mg/kg/天)。结果发现,它可降低小鼠中动脉瘤(从 72%降至 45%)、夹层(从 17%降至 10%)和破裂(从 33%降至 15%)的发生率。与未给予槲皮素治疗的小鼠相比,用槲皮素治疗的小鼠中的弹性蛋白降解得到改善(降解评分 2.9 ± 0.3 对 2.2 ± 0.2)。此外,槲皮素抑制了血管细胞黏附分子-1 的表达、巨噬细胞浸润和促基质金属蛋白酶-9 活性。我们的结果表明,槲皮素可能通过其抗炎和内皮细胞保护作用预防动脉粥样硬化相关的急性主动脉综合征的发生。