Quercetin Downregulates Cyclooxygenase-2 Expression and HIF-1?/VEGF Signaling-Related Angiogenesis in a Mouse Model of Abdominal Aortic Aneurysm.

ABSTRACT: Objective:Abdominal aortic aneurysm (AAA) development has been characterized by increased expression of vascular endothelial growth factor (VEGF), which contributes to angiogenesis via cyclooxygenase-2 (COX-2). Quercetin, one of the most common and well-researched flavonoids and abundant in vegetables and fruits, has beneficial effects in inhibiting angiogenesis. This study investigated the antiangiogenic effects of quercetin on experimental aneurysms. Methods:We utilized the in vivo AAA mouse model induced by the periaortic application of CaCl2 to examine the effectiveness of quercetin in blocking angiogenesis. Quercetin was administered at 60?mg/kg once daily on the day of the AAA induction and then continued for 6 weeks. Celecoxib, a selective COX-2 inhibitor, was used as the positive control. Results:Our results demonstrated that quercetin significantly attenuated aneurysm growth in AAA mice and medial neovascularization. Accordingly, quercetin decreased the expression of proangiogenic mediators, including VEGF-A, intercellular adhesion molecule-1, vascular cell adhesion molecule 1, and vascular endothelial cadherin. Quercetin treatment also inhibited the expression of COX-2 and hypoxia-inducible factor 1? (HIF-1?). It was also found that quercetin-3-glucuronide, a major quercetin metabolite, downregulated the expression of COX-2, HIF-1?, VEGF-A, and matrix metalloproteinase activities in aortic vascular smooth muscle cells isolated from AAA mice. Conclusion:Quercetin attenuates neovascularization during AAA growth, and this effect is mediated via the inhibition of COX-2, which decreases HIF-1?/VEGF signaling-related angiogenesis.

SUBMITTER: Wang L 

PROVIDER: S-EPMC7463408 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature