Upregulation of miR-223 abrogates NLRP3 inflammasome-mediated pyroptosis to attenuate oxidized low-density lipoprotein (ox-LDL)-induced cell death in human vascular endothelial cells (ECs).

MiR-223 is closely associated with pathogenesis of coronary artery disease (CAD); however, the molecular mechanisms are unclear. In the present study, the human vascular endothelial cells (ECs) were isolated from patients undergoing coronary artery bypass graft and treated with oxidized low-density lipoprotein (ox-LDL) to induce cellular CAD models in vitro. We found that ox-LDL inhibited cell proliferation and viability, and promoted cell apoptosis in ECs. Of note, ox-LDL promoted cell pyroptosis, and both the pyroptosis inhibitor necrosulfonamide (NSA) and NLRP3 ablation restored cell viability in ECs treated with ox-LDL, indicating that ox-LDL induced EC death by triggering cell pyroptosis. In addition, miR-223 was downregulated by ox-LDL in ECs, and miR-223 overexpression rescued cell viability in ECs treated with ox-LDL. Interestingly, there existed targeting sites in miR-223 and 3' untranslated regions (3' UTRs) of NLRP3 mRNA, and further experiments validated that miR-223 negatively regulated NLRP3 expressions in ECs at both transcriptional and translational levels. Finally, we verified that upregulation of NLRP3 abrogated the protective effects of miR-223 overexpression on ox-LDL-treated ECs. Collectively, this in vitro study proved that overexpression of miR-223 protected ox-LDL-stimulated ECs from death through inactivating NLRP3 inflammasome-mediated pyroptotic cell death.