Department of Cardiology, Fuwai Yunnan Hospital, Chinese Academy of Medical Sciences, Affiliated Cardiovascular Hospital of Kunming Medical University, Kunming, China.
Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical Colleg, Beijing, China.
J Biochem Mol Toxicol. 2024 Nov;38(11):e70011. doi: 10.1002/jbt.70011.
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.
冠状动脉疾病（CAD）导致心肌缺血，管腔变窄或闭塞。尽管 CAD 的治疗取得了很大进展，但现有的治疗方法仍不能满足临床需求，因此迫切需要寻找新的治疗方法。本研究旨在通过抑制血管内皮细胞损伤来探讨 miR-148a-3p 缓解 CAD 的作用机制，为 CAD 的治疗提供新的思路。通过脂多糖（LPS）诱导血管内皮细胞构建细胞模型，通过高脂肪饮食和脑垂体后叶素腹腔注射建立 CAD 大鼠模型。通过 RT-qPCR、ELISA、Western blot、MTT 和流式细胞术检测相关指标。结果表明，在 LPS 诱导的血管内皮细胞实验中，miR-148a-3p 抑制了 PCSK9 的上调，从而抑制了 NF-κB 信号通路并促进了血管内皮细胞的增殖。过表达 PCSK9 并添加 NF-κB 信号通路激活剂增加了血管内皮细胞的凋亡。在动物实验中，miR-148a-3p 缓解了 CAD 大鼠的症状，而过表达 PCSK9 则促进了 CAD 大鼠的细胞凋亡并增加了动脉粥样硬化斑块面积。综上所述，miR-148a-3p 通过下调 PCSK9 抑制 NF-κB 信号通路，从而保护血管内皮细胞，缓解 CAD。
