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Diabetes mellitus is commonly recognized as a significantly and independently risk factor for atherosclerotic disease. However, the mechanisms of high glucose leading to atherosclerosis is unclear. The purpose of this study was to investigate whether high glucose enhances an innate immune response through activating the NLRP3 inflammasome in vascular endothelial cells, that contributes to atherosclerotic lesions.
We prescribed high glucose to treat human umbilical vein endothelial cells (HUVECs). The diabetes mellitus model animals were established by chemical induction method in ApoE-/- mice. The lentivirus transfection technology was used to knock down the Nlrp3 gene expression. The immune response and atherosclerotic pathological changes were observed by real-time PCR, western blot, enzyme-linked immunosorbent assay, and histology staining methods.
The expression of NLRP3 inflammasome (including NLRP3, Caspase-1 and ASC), and subsequently the inflammatory cytokine (IL-1β) were increased by D-glucose in a dose- and time-dependent manner, peaking at 35.5 mM with 7 days. After knocking down the Nlrp3 gene, the expression of IL-1βsignificantly decreased with the NLRP3 inflammasome (NLRP3, Caspase-1 and ASC) weakened although high glucose existence. And the adhesion molecules (ICAM-1 and VCAM-1) expression significantly reduced following. Consequently, the atherosclerotic lesions were obviously lightened in aorta.
High glucose induced atherosclerosis in endothelium via NLRP3 inflammasome activation. This enhanced innate immunity in endothelium to cause atherosclerotic lesions.