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

doi:10.12307/2023.773

Abstract

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.

Key words: dapagliflozin, pyroptosis, oxidized low-density lipoprotein, NLRP3 inflammasome, human umbilical vein endothelial cell, endothelial cell function, atherosclerosis

CLC Number:

Zhao Quanwei, Li Hui, Liu Danan, Gong Caiwei, Chen Long. Dapagliflozin attenuates endothelial cell pyroptosis and dysfunction induced by oxidized low-density lipoprotein[J]. Chinese Journal of Tissue Engineering Research, 2024, 28(1): 80-85.

Figures/Tables 5

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