miR‐148a‐3p mitigation of coronary artery disease through PCSK9/NF‐κB inhibition of vascular endothelial cell injury

Coronary artery disease (CAD) causes myocardial ischemia, narrowing or occlusion of the lumen. Although great progress has been made in the treatment of CAD, the existing treatment methods do not meet the clinical needs, so it is urgent to find new treatment methods. The aim of this study was to investigate the mechanism of action of miR-148a-3p in alleviating CAD by inhibiting vascular endothelial cell injury and to provide new ideas for the treatment of CAD. A cell model was constructed by lipopolysaccharide (LPS) induction of vascular endothelial cells, and a CAD rat model was established by a high-fat diet and intraperitoneal injection of posterior pituitary hormone. Relevant indices were detected by RT-qPCR, ELISA, Western blot, MTT, and flow cytometry. The results indicate that in LPS-induced vascular endothelial cell assays, miR-148a-3p inhibited the upregulation of PCSK9, thereby suppressing the NF-κB signaling pathway and promoting vascular endothelial cell proliferation. Overexpression of PCSK9 and the addition of NF-κB signaling pathway activator increased vascular endothelial cell apoptosis. In animal experiments, miR-148a-3p alleviated the symptoms of CAD rats, whereas overexpression of PCSK9 promoted apoptosis and increased atheromatous plaque area in CAD rats. In conclusion, miR-148a-3p inhibits the NF-κB signaling pathway through downregulation of PCSK9, thereby protecting vascular endothelial cells and alleviating CAD.