TY - JOUR
T1 - Preventive effects of quercetin against the onset of atherosclerosis-related acute aortic syndromes in mice
AU - Kondo, Masateru
AU - Izawa-Ishizawa, Yuki
AU - Goda, Mitsuhiro
AU - Hosooka, Mayuko
AU - Kagimoto, Yuu
AU - Saito, Naoko
AU - Matsuoka, Rie
AU - Zamami, Yoshito
AU - Chuma, Masayuki
AU - Yagi, Kenta
AU - Takechi, Kenshi
AU - Tsuneyama, Koichi
AU - Ishizawa, Keisuke
N1 - Funding Information:
This work was supported by grants from JSPS KAKENHI Grant Number, JP16K08549 (Y.I.-I.), and JP 18K06686 (K.I.).
Funding Information:
Funding: This work was supported by grants from JSPS KAKENHI Grant Number, JP16K08549 (Y.I.-I.), and JP 18K06686 (K.I.).
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/10/1
Y1 - 2020/10/1
N2 - 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.
AB - 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.
KW - Aortic aneurysm
KW - Aortic dissection
KW - Endothelial dysfunction
KW - Flavonoids
KW - Inflammation
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U2 - 10.3390/ijms21197226
DO - 10.3390/ijms21197226
M3 - Article
C2 - 33007902
AN - SCOPUS:85091999803
SN - 1661-6596
VL - 21
SP - 1
EP - 13
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 19
M1 - 7226
ER -