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Int J Mol Sci ; 21(19)2020 Sep 30.
Article in English | MEDLINE | ID: mdl-33007902

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 ß-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.


Subject(s)
Aortic Aneurysm/drug therapy , Aortic Dissection/drug therapy , Atherosclerosis/drug therapy , Hypertension/drug therapy , Quercetin/pharmacology , Aminopropionitrile/adverse effects , Aortic Dissection/chemically induced , Aortic Dissection/complications , Aortic Dissection/pathology , Angiotensin II/adverse effects , Animals , Aorta, Thoracic/drug effects , Aortic Aneurysm/chemically induced , Aortic Aneurysm/complications , Aortic Aneurysm/pathology , Atherosclerosis/genetics , Atherosclerosis/pathology , Blood Pressure/drug effects , Disease Models, Animal , Humans , Hypertension/chemically induced , Hypertension/complications , Hypertension/pathology , Mice , Protein-Lysine 6-Oxidase/antagonists & inhibitors
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