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

Int J Mol Sci. 2020 Sep 30;21(19):7226. 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.

Keywords: aortic aneurysm; aortic dissection; endothelial dysfunction; flavonoids; inflammation.

MeSH terms

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

Substances

  • Angiotensin II
  • Aminopropionitrile
  • Quercetin
  • Protein-Lysine 6-Oxidase