Background: 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 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.
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 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.
Conclusions: 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.
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http://dx.doi.org/10.23736/S2724-5683.24.06604-3 | DOI Listing |
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