Procyanidin B2 mitigates endothelial endoplasmic reticulum stress through a PPARδ-Dependent mechanism
Hyperglycemia-induced endothelial endoplasmic reticulum (ER) stress is implicated in the pathophysiology of diabetes and its vascular complications. Procyanidins are enriched in many plant foods and have been demonstrated to exert several beneficial effects on diabetes, cardiovascular and other meta...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-10-01
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| Series: | Redox Biology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231720309332 |
| _version_ | 1818647268915412992 |
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| author | Xin Nie Weiqi Tang Zihui Zhang Chunmiao Yang Lei Qian Xinya Xie Erjiao Qiang Jingyang Zhao Wenfei Zhao Lei Xiao Nanping Wang |
| author_facet | Xin Nie Weiqi Tang Zihui Zhang Chunmiao Yang Lei Qian Xinya Xie Erjiao Qiang Jingyang Zhao Wenfei Zhao Lei Xiao Nanping Wang |
| author_sort | Xin Nie |
| collection | DOAJ |
| description | Hyperglycemia-induced endothelial endoplasmic reticulum (ER) stress is implicated in the pathophysiology of diabetes and its vascular complications. Procyanidins are enriched in many plant foods and have been demonstrated to exert several beneficial effects on diabetes, cardiovascular and other metabolic diseases. In the present study, we investigated the effect of procyanidin B2 (PCB2), the most widely distributed natural procyanidin, on ER stress evoked by high glucose in endothelial cells (ECs) and the underlying mechanisms. We showed that PCB2 mitigated the high glucose-activated ER stress pathways (PERK, IRE1α and ATF6) in human vascular ECs. In addition, we found that PCB2 attenuated endothelial ER stress via the activation of peroxisome proliferator-activated receptor δ (PPARδ). We demonstrated that PCB2 directly bound to and activated PPARδ. Conversely, GSK0660, a selective PPARδ antagonist, attenuated the suppressive effect of PCB2 on the ER stress signal pathway. Functionally, PCB2 ameliorated the high glucose-impaired endothelium-dependent relaxation in mouse aortas. The protective effect of PCB2 on vasodilation was abolished in the aortas pretreated with GSK0660 or those from the EC-specific PPARδ knockout mice. Moreover, the protective effects of PCB2 on ER stress and endothelial dysfunction required the inter-dependent actions of PPARδ and AMPK. Collectively, we demonstrated that PCB2 mitigated ER stress and ameliorated vasodilation via a PPARδ-mediated mechanism beyond its classic action as a scavenger of free radicals. These findings further highlighted the novel roles of procyanidins in intervening the ER stress and metabolic disorders related to endothelial dysfunction. |
| first_indexed | 2024-12-17T00:59:50Z |
| format | Article |
| id | doaj.art-462662b78f93419ebe3d8e155d6c1b19 |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-12-17T00:59:50Z |
| publishDate | 2020-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-462662b78f93419ebe3d8e155d6c1b192022-12-21T22:09:30ZengElsevierRedox Biology2213-23172020-10-0137101728Procyanidin B2 mitigates endothelial endoplasmic reticulum stress through a PPARδ-Dependent mechanismXin Nie0Weiqi Tang1Zihui Zhang2Chunmiao Yang3Lei Qian4Xinya Xie5Erjiao Qiang6Jingyang Zhao7Wenfei Zhao8Lei Xiao9Nanping Wang10Advanced Institute for Medical Sciences, Dalian Medical University, Dalian, 116044, ChinaAdvanced Institute for Medical Sciences, Dalian Medical University, Dalian, 116044, China; Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, 710061, ChinaCardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, 710061, ChinaCardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, 710061, ChinaAdvanced Institute for Medical Sciences, Dalian Medical University, Dalian, 116044, ChinaCardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, 710061, ChinaAdvanced Institute for Medical Sciences, Dalian Medical University, Dalian, 116044, ChinaAdvanced Institute for Medical Sciences, Dalian Medical University, Dalian, 116044, China; Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, 710061, ChinaCardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, 710061, ChinaCardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, 710061, China; Corresponding author. Cardiovascular Research Center, Xi'an Jiaotong University, Xi'an, 710061, China.Advanced Institute for Medical Sciences, Dalian Medical University, Dalian, 116044, China; Corresponding author.Hyperglycemia-induced endothelial endoplasmic reticulum (ER) stress is implicated in the pathophysiology of diabetes and its vascular complications. Procyanidins are enriched in many plant foods and have been demonstrated to exert several beneficial effects on diabetes, cardiovascular and other metabolic diseases. In the present study, we investigated the effect of procyanidin B2 (PCB2), the most widely distributed natural procyanidin, on ER stress evoked by high glucose in endothelial cells (ECs) and the underlying mechanisms. We showed that PCB2 mitigated the high glucose-activated ER stress pathways (PERK, IRE1α and ATF6) in human vascular ECs. In addition, we found that PCB2 attenuated endothelial ER stress via the activation of peroxisome proliferator-activated receptor δ (PPARδ). We demonstrated that PCB2 directly bound to and activated PPARδ. Conversely, GSK0660, a selective PPARδ antagonist, attenuated the suppressive effect of PCB2 on the ER stress signal pathway. Functionally, PCB2 ameliorated the high glucose-impaired endothelium-dependent relaxation in mouse aortas. The protective effect of PCB2 on vasodilation was abolished in the aortas pretreated with GSK0660 or those from the EC-specific PPARδ knockout mice. Moreover, the protective effects of PCB2 on ER stress and endothelial dysfunction required the inter-dependent actions of PPARδ and AMPK. Collectively, we demonstrated that PCB2 mitigated ER stress and ameliorated vasodilation via a PPARδ-mediated mechanism beyond its classic action as a scavenger of free radicals. These findings further highlighted the novel roles of procyanidins in intervening the ER stress and metabolic disorders related to endothelial dysfunction.http://www.sciencedirect.com/science/article/pii/S2213231720309332Endoplasmic reticulum stressProcyanidin B2Peroxisome proliferator-activated receptor δEndothelium-dependent relaxation |
| spellingShingle | Xin Nie Weiqi Tang Zihui Zhang Chunmiao Yang Lei Qian Xinya Xie Erjiao Qiang Jingyang Zhao Wenfei Zhao Lei Xiao Nanping Wang Procyanidin B2 mitigates endothelial endoplasmic reticulum stress through a PPARδ-Dependent mechanism Redox Biology Endoplasmic reticulum stress Procyanidin B2 Peroxisome proliferator-activated receptor δ Endothelium-dependent relaxation |
| title | Procyanidin B2 mitigates endothelial endoplasmic reticulum stress through a PPARδ-Dependent mechanism |
| title_full | Procyanidin B2 mitigates endothelial endoplasmic reticulum stress through a PPARδ-Dependent mechanism |
| title_fullStr | Procyanidin B2 mitigates endothelial endoplasmic reticulum stress through a PPARδ-Dependent mechanism |
| title_full_unstemmed | Procyanidin B2 mitigates endothelial endoplasmic reticulum stress through a PPARδ-Dependent mechanism |
| title_short | Procyanidin B2 mitigates endothelial endoplasmic reticulum stress through a PPARδ-Dependent mechanism |
| title_sort | procyanidin b2 mitigates endothelial endoplasmic reticulum stress through a pparδ dependent mechanism |
| topic | Endoplasmic reticulum stress Procyanidin B2 Peroxisome proliferator-activated receptor δ Endothelium-dependent relaxation |
| url | http://www.sciencedirect.com/science/article/pii/S2213231720309332 |
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