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.

MiR-223与冠状动脉疾病（CAD）的发病机理密切相关；但是，分子机制尚不清楚。在本研究中，从进行冠状动脉搭桥术的患者中分离人血管内皮细胞（EC），并用氧化的低密度脂蛋白（ox-LDL）处理以在体外诱导细胞CAD模型。我们发现ox-LDL抑制EC的细胞增殖和活力，并促进细胞凋亡。值得注意的是，ox-LDL促进了细胞的凋亡，并且凋亡抑制剂坏死磺酰胺（NSA）和NLRP3消融均恢复了用ox-LDL处理的EC的细胞活力，表明ox-LDL通过触发细胞凋亡来诱导EC死亡。另外，oxR-DLL在ECs中下调了miR-223，miR-223的过表达挽救了用Ox-LDL处理的ECs中的细胞活力。有趣的是 在miR-223和NLRP3 mRNA的3'非翻译区（3'UTR）中存在靶向位点，进一步的实验验证了miR-223在转录和翻译水平上均负调控EC中的NLRP3表达。最后，我们验证了NLRP3的上调消除了miR-223过表达对ox-LDL处理的EC的保护作用。总的来说，这项体外研究证明，miR-223的过表达通过灭活NLRP3炎性体介导的焦细胞凋亡来保护ox-LDL刺激的EC免受死亡。我们证实NLRP3的上调消除了miR-223过表达对经ox-LDL处理的EC的保护作用。总的来说，这项体外研究证明，miR-223的过表达通过灭活NLRP3炎性体介导的焦细胞凋亡来保护ox-LDL刺激的EC免受死亡。我们证实NLRP3的上调消除了miR-223过表达对经ox-LDL处理的EC的保护作用。总的来说，这项体外研究证明，miR-223的过表达通过灭活NLRP3炎性体介导的焦细胞凋亡来保护ox-LDL刺激的EC免受死亡。