Carvedilol ameliorates experimental atherosclerosis by inhibiting the NLRP3 inflammasome.

Abstract

To investigate the protective effect of carvedilol against atherosclerosis by inhibiting the NLRP3 inflammasome. In-vitro experiments, human umbilical vein endothelial cells (HUVEC) were divided into the control group, ox-LDL group, carvedilol 5 μM group, carvedilol 10 μM group, and carvedilol 20 μM 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 5 μM (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. 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 5 μM, 10 μM, and 20 μM 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. Carvedilol effectively inhibits the progression of atherosclerosis by targeting the NLRP3 inflammasome, thereby providing valuable mechanistic insights into its beneficial effects on atherosclerotic cardiovascular disease.