Quercetin Downregulates Cyclooxygenase-2 Expression and HIF-1α/VEGF Signaling-Related Angiogenesis in a Mouse Model of Abdominal Aortic Aneurysm
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 vegetab...
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doaj-6e3e31de8ef24f45b57aaa05d993b5d32020-11-25T02:54:22ZengHindawi LimitedBioMed Research International2314-61332314-61412020-01-01202010.1155/2020/94853989485398Quercetin Downregulates Cyclooxygenase-2 Expression and HIF-1α/VEGF Signaling-Related Angiogenesis in a Mouse Model of Abdominal Aortic AneurysmLian Wang0Haiwei Wu1Lei Xiong2Xiaolong Liu3Nan Yang4Liguo Luo5Tao Qin6Xian Zhu7Zhonghua Shen8Hua Jing9Jinming Chen10Department of Thoracic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, ChinaDepartment of Cardiothoracic Surgery, Jingling Hospital, Clinical Medicine School of Nanjing University, Nanjing 210002, ChinaDepartment of Cardiothoracic Surgery, Jingling Hospital, Clinical Medicine School of Nanjing University, Nanjing 210002, ChinaDepartment of Cardiothoracic Surgery, Jingling Hospital, Clinical Medicine School of Nanjing University, Nanjing 210002, ChinaDepartment of Cardiothoracic Surgery, Jingling Hospital, Clinical Medicine School of Nanjing University, Nanjing 210002, ChinaDepartment of Cardiothoracic Surgery, Jingling Hospital, Clinical Medicine School of Nanjing University, Nanjing 210002, ChinaDepartment of Cardiothoracic Surgery, Jingling Hospital, Clinical Medicine School of Nanjing University, Nanjing 210002, ChinaDepartment of Cardiac Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, ChinaDepartment of Cardiac Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, ChinaDepartment of Cardiothoracic Surgery, Jingling Hospital, Clinical Medicine School of Nanjing University, Nanjing 210002, ChinaDepartment of Anorectal Surgery, The Third People’s Hospital of Hangzhou, Hangzhou 310009, ChinaObjective. 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 1α (HIF-1α). It was also found that quercetin-3-glucuronide, a major quercetin metabolite, downregulated the expression of COX-2, HIF-1α, 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-1α/VEGF signaling-related angiogenesis.http://dx.doi.org/10.1155/2020/9485398 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Lian Wang Haiwei Wu Lei Xiong Xiaolong Liu Nan Yang Liguo Luo Tao Qin Xian Zhu Zhonghua Shen Hua Jing Jinming Chen |
spellingShingle |
Lian Wang Haiwei Wu Lei Xiong Xiaolong Liu Nan Yang Liguo Luo Tao Qin Xian Zhu Zhonghua Shen Hua Jing Jinming Chen Quercetin Downregulates Cyclooxygenase-2 Expression and HIF-1α/VEGF Signaling-Related Angiogenesis in a Mouse Model of Abdominal Aortic Aneurysm BioMed Research International |
author_facet |
Lian Wang Haiwei Wu Lei Xiong Xiaolong Liu Nan Yang Liguo Luo Tao Qin Xian Zhu Zhonghua Shen Hua Jing Jinming Chen |
author_sort |
Lian Wang |
title |
Quercetin Downregulates Cyclooxygenase-2 Expression and HIF-1α/VEGF Signaling-Related Angiogenesis in a Mouse Model of Abdominal Aortic Aneurysm |
title_short |
Quercetin Downregulates Cyclooxygenase-2 Expression and HIF-1α/VEGF Signaling-Related Angiogenesis in a Mouse Model of Abdominal Aortic Aneurysm |
title_full |
Quercetin Downregulates Cyclooxygenase-2 Expression and HIF-1α/VEGF Signaling-Related Angiogenesis in a Mouse Model of Abdominal Aortic Aneurysm |
title_fullStr |
Quercetin Downregulates Cyclooxygenase-2 Expression and HIF-1α/VEGF Signaling-Related Angiogenesis in a Mouse Model of Abdominal Aortic Aneurysm |
title_full_unstemmed |
Quercetin Downregulates Cyclooxygenase-2 Expression and HIF-1α/VEGF Signaling-Related Angiogenesis in a Mouse Model of Abdominal Aortic Aneurysm |
title_sort |
quercetin downregulates cyclooxygenase-2 expression and hif-1α/vegf signaling-related angiogenesis in a mouse model of abdominal aortic aneurysm |
publisher |
Hindawi Limited |
series |
BioMed Research International |
issn |
2314-6133 2314-6141 |
publishDate |
2020-01-01 |
description |
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 1α (HIF-1α). It was also found that quercetin-3-glucuronide, a major quercetin metabolite, downregulated the expression of COX-2, HIF-1α, 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-1α/VEGF signaling-related angiogenesis. |
url |
http://dx.doi.org/10.1155/2020/9485398 |
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