NLRP3 inflammasome promotes diabetes-induced endothelial inflammation and atherosclerosis

被引：78

作者：

Wan, Zhaofei ^{[1
]}

Fan, Yan ^{[2
]}

Liu, Xiaojun ^{[1
]}

Xue, Jiahong ^{[1
]}

Han, Zhenhua ^{[1
]}

Zhu, Canzhan ^{[1
]}

Wang, Xinhong ^{[1
]}

机构：

[1] Xi An Jiao Tong Univ, Med Coll, Dept Cardiovasc Med, Affiliated Hosp 2, 157 Xiwu Rd, Xian 710004, Shaanxi, Peoples R China

[2] Gansu Prov Hosp, Dept Cardiovasc Med, Lanzhou, Gansu, Peoples R China

来源：

DIABETES METABOLIC SYNDROME AND OBESITY-TARGETS AND THERAPY | 2019年 / 12卷

关键词：

NLRP3; inflammasome; diabetes; atherosclerosis; inflammation; ACTIVATION; EXPRESSION; MONOCYTES; CELLS; ATHEROGENESIS; OBESITY;

D O I：

10.2147/DMSO.S222053

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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-1 beta 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-1 beta level were significantly higher in diabetes patients but considerably decreased after lifestyle interventions and medicine. Moreover, carotid atherosclerosis was significantly related to plasma IL-1 beta 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-1 beta were augmented by high glucose in HUVECs. Moreover, either high glucose or IL-1 beta promoted the expression of adhesion molecules, which were suppressed by NLRP3 knockdown or IL-1 beta receptor antagonist. Conclusion: These findings provide novel insights into pathological mechanisms of diabetic atherosclerosis and have potential therapeutic implications for cardiovascular complications in diabetes.

引用

页码：1931 / 1942

页数：12

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