NLRP3 inflammasome promotes diabetes-induced endothelial inflammation and atherosclerosis
Zhaofei Wan,1 Yan Fan,2 Xiaojun Liu,1 Jiahong Xue,1 Zhenhua Han,1 Canzhan Zhu,1 Xinhong Wang1 1Department of Cardiovascular Medicine, Second Affiliated Hospital of Medical College, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2Department of Car...
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| Autores principales: | , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
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Dove Medical Press
2019
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| Acceso en línea: | https://doaj.org/article/badb9efce61a42c18bb26c0134bbefbf |
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| Sumario: | Zhaofei Wan,1 Yan Fan,2 Xiaojun Liu,1 Jiahong Xue,1 Zhenhua Han,1 Canzhan Zhu,1 Xinhong Wang1 1Department of Cardiovascular Medicine, Second Affiliated Hospital of Medical College, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2Department of Cardiovascular Medicine, Gansu Provincial Hospital, Lanzhou, People’s Republic of ChinaCorrespondence: Xinhong WangDepartment of Cardiovascular Medicine, Second Affiliated Hospital of Medical College, Xi’an Jiaotong University, 157 Xiwu Road, Xi’an, Shaanxi 710004, People’s Republic of ChinaTel +86 298 632 0430Email wangxinhongshx@163.comBackground: NLRP3 inflammasome can be activated by high glucose and links inflammation and metabolic disease. This study aimed to investigate the role of NLRP3 inflammasome in hyperglycemia-induced endothelial inflammation and diabetic atherosclerosis.Methods: NLRP3 levels in peripheral blood mononuclear cell (PBMC) and plasma IL-1β level were measured in diabetes patients. The activation of NLPR3 was detected in diabetic ApoE−/− mice and human umbilical vein endothelial cells (HUVECs).Results: Compared with healthy controls, NLRP3 expression levels in PBMC and plasma IL-1β level were significantly higher in diabetes patients but considerably decreased after lifestyle interventions and medicine. Moreover, carotid atherosclerosis was significantly related to plasma IL-1β level in diabetes patients. In diabetic atherosclerosis mouse model, NLRP3 knockdown suppressed NLRP3 inflammasome activation, inhibited the expression of adhesion molecules ICAM-1 and VCAM-1 in intima, reduced atherosclerosis and stabilized atherosclerotic plaque. In vitro, the expression of NLRP3 inflammasome components and the secretion of IL-1β were augmented by high glucose in HUVECs. Moreover, either high glucose or IL-1β promoted the expression of adhesion molecules, which were suppressed by NLRP3 knockdown or IL-1β receptor antagonist.Conclusion: These findings provide novel insights into pathological mechanisms of diabetic atherosclerosis and have potential therapeutic implications for cardiovascular complications in diabetes.Keywords: NLRP3 inflammasome, diabetes, atherosclerosis, inflammation |
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