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:	Wan Z, Fan Y, Liu X, Xue J, Han Z, Zhu C, Wang X
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	NLRP3 inflammasome diabetes atherosclerosis inflammation Specialties of internal medicine RC581-951
Acceso en línea:	https://doaj.org/article/badb9efce61a42c18bb26c0134bbefbf
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spelling	oai:doaj.org-article:badb9efce61a42c18bb26c0134bbefbf2021-12-02T06:42:05ZNLRP3 inflammasome promotes diabetes-induced endothelial inflammation and atherosclerosis1178-7007https://doaj.org/article/badb9efce61a42c18bb26c0134bbefbf2019-09-01T00:00:00Zhttps://www.dovepress.com/nlrp3-inflammasome-promotes-diabetes-induced-endothelial-inflammation--peer-reviewed-article-DMSOhttps://doaj.org/toc/1178-7007Zhaofei 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, inflammationWan ZFan YLiu XXue JHan ZZhu CWang XDove Medical PressarticleNLRP3 inflammasomediabetesatherosclerosisinflammationSpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 12, Pp 1931-1942 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	NLRP3 inflammasome diabetes atherosclerosis inflammation Specialties of internal medicine RC581-951
spellingShingle	NLRP3 inflammasome diabetes atherosclerosis inflammation Specialties of internal medicine RC581-951 Wan Z Fan Y Liu X Xue J Han Z Zhu C Wang X NLRP3 inflammasome promotes diabetes-induced endothelial inflammation and atherosclerosis
description	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
format	article
author	Wan Z Fan Y Liu X Xue J Han Z Zhu C Wang X
author_facet	Wan Z Fan Y Liu X Xue J Han Z Zhu C Wang X
author_sort	Wan Z
title	NLRP3 inflammasome promotes diabetes-induced endothelial inflammation and atherosclerosis
title_short	NLRP3 inflammasome promotes diabetes-induced endothelial inflammation and atherosclerosis
title_full	NLRP3 inflammasome promotes diabetes-induced endothelial inflammation and atherosclerosis
title_fullStr	NLRP3 inflammasome promotes diabetes-induced endothelial inflammation and atherosclerosis
title_full_unstemmed	NLRP3 inflammasome promotes diabetes-induced endothelial inflammation and atherosclerosis
title_sort	nlrp3 inflammasome promotes diabetes-induced endothelial inflammation and atherosclerosis
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/badb9efce61a42c18bb26c0134bbefbf
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_version_	1718399775630426112

NLRP3 inflammasome promotes diabetes-induced endothelial inflammation and atherosclerosis

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