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NLRP3 inflammasome promotes diabetes-induced endothelial inflammation and atherosclerosis

Authors Wan Z, Fan Y, Liu X, Xue J, Han Z, Zhu C, Wang X

Received 5 July 2019

Accepted for publication 26 August 2019

Published 20 September 2019 Volume 2019:12 Pages 1931—1942

DOI https://doi.org/10.2147/DMSO.S222053

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Nicola Ludin

Peer reviewer comments 2

Editor who approved publication: Dr Juei-Tang Cheng


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 China

Correspondence: Xinhong Wang
Department of Cardiovascular Medicine, Second Affiliated Hospital of Medical College, Xi’an Jiaotong University, 157 Xiwu Road, Xi’an, Shaanxi 710004, People’s Republic of China
Tel +86 298 632 0430
Email wangxinhongshx@163.com

Background: 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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