Dapagliflozin attenuates endothelial cell pyroptosis and dysfunction induced by oxidized low-density lipoprotein

Zhao Quanwei; Li Hui; Liu Danan; Gong Caiwei; Chen Long

doi:10.12307/2023.773

Abstract：BACKGROUND:Dapagliflozin,an inhibitor of sodium-glucose cotransporter 2,can delay the progression of atherosclerosis by regulating glucose metabolism,inhibiting inflammation and improving endothelial cell function. OBJECTIVE:To study the effect of dapagliflozin on cell pyroptosis and endothelial dysfunction induced by oxidized low-density lipoprotein. METHODS:Human umbilical vein endothelial cells were divided into a control group(no intervention),a model group(treated with oxidized low-density lipoprotein for 24 hours),and a dapagliflozin group(treated with oxidized low-density lipoprotein + dapagliflozin for 24 hours).Endothelial cell proliferation activity was measured by cell counting kit-8 assay.The levels of intercellular adhesion molecule 1,vascular cell adhesion molecule 1,and monocyte chemotactic protein-1 in cell supernatant were detected using ELISA.Nitric oxide level in the cells was detected by nitrate reductase assay.The pyroptosis rate and characteristics of endothelial cells were detected by Hoechst 33342/PI fluorescence co-staining and lactate dehydrogenase release assay.The protein expression levels of NLRP3,caspase-1,GSDMD,interleukin-1β,and interleukin-18 were detected by western blot assay. RESULTS AND CONCLUSION:(1)Oxidized low-density lipoprotein could cause pyroptosis and dysfunction of endothelial cells.(2)Compared with the control group,the level of nitric oxide and cell activity were decreased(P<0.05),while lactate dehydrogenase,intercellular adhesion molecule 1,vascular cell adhesion molecule 1,and monocyte chemotactic protein-1 levels were significantly increased in the model group(P<0.05).Compared with the model group,cell activity and nitric oxide levels significantly increased(P<0.05),but lactate dehydrogenase,intercellular adhesion molecule 1,vascular cell adhesion molecule 1,and monocyte chemotactic protein-1 levels were significantly diminished in the dapagliflozin group(P<0.05).(3)Compared with the model group,cell pyroptosis rate and the protein expression of pyroptosis factor NLRP3,caspase-1,GSDMD,interleukin-18 and interleukin-1β significantly reduced in the dapagliflozin group(P<0.05).(4)The results indicate that dapagliflozin inhibits oxidized low-density lipoprotein-induced endothelial pyroptosis and ameliorates endothelial cell dysfunction.