Abstract
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.