Carvedilol ameliorates experimental atherosclerosis by inhibiting the NLRP3 inflammasome

Abstract

Abstract Objective: To investigate the protective effect of carvedilol against atherosclerosis by inhibiting the NLRP3 inflammasome. Methods：In vitro experiments, human umbilical vein endothelial cells(HUVEC) were divided into the control group, ox-LDL group, carvedilol 5μM group, carvedilol 10μM group, and carvedilol 20μM group. The optimal concentration of carvedilol was determined using the CCK-8 method to assess cell proliferation levels and oil red O staining to observe intracellular lipid droplet formation. Subsequently, the cells were further divided into the control group, ox-LDL group, carvedilol 5μM (optimal concentration) group, and MCC950 (inhibitor of NLRP3 Inflammasome) group. The expression levels of intracellular proteins NLRP3, pro-Caspase-1, Caspase1, pro-IL-1β, IL-1β, p65, GSDMD, and N-GSDMD were detected by ELISA, or Western Blotting. Results: Compared to the control group, the ox-LDL group exhibited a significant reduction in cell proliferation level (P<0.05), accompanied by an increase in lipid droplet formation upon induction. In contrast, pretreatment with carvedilol at concentrations of 5μM, 10μM, and 20μM effectively promoted cell proliferation (P<0.05) and inhibited intracellular lipid droplet formation. Notably, the most pronounced effect was observed with carvedilol pretreatment at a concentration of 5μM. Furthermore, compared to the control group, HUVEC cells in the ox-LDL group demonstrated substantial upregulation of NLRP3, pro-Caspase-1, Caspase1, pro-IL-1β, IL-1β, p65 GSDMD and N-GSDMD; however, these markers were downregulated following treatment with carvedilol and MCC950 administration-particularly evident in the carvedilol group. Conclusion: Carvedilol effectively inhibits the progression of atherosclerosisby targeting the NLRP3 inflammasome, thereby providing valuable mechanistic insights into its beneficial effects on atherosclerotic cardiovascular disease.