Chen Jinhe, Liu Fan, Meng Xianwei
Department of Cardiovascular Medicine, Yantai Yantaishan Hospital, Yantai, Shandong, China.
Fuwai Yunnan Hospital, Chinese Academy of Medical Sciences, Kunming, Yunnan, China.
Biochem Genet. 2024 Dec 28. doi: 10.1007/s10528-024-10998-w.
Recent studies highlight the crucial role of microRNAs (miRNAs) in coronary artery disease (CAD). This retrospective study investigated the abundance of miR-432-5p in the serum of CAD patients and explored its role. 252 volunteers were included. The levels of miR-432-5p and Sortilin 1 (SORT1) in the serum of CAD patients and oxidized low-density lipoprotein (ox-LDL)-treated human arterial smooth muscle cells (HASMCs) were quantified via qRT-PCR. The correlation coefficient, clinical diagnostic performance, and risk factors were analyzed with Pearson correlation, receiver operating characteristic (ROC) curve, and binomial logistic regression, respectively. HASMC proliferation, migration, and apoptosis were evaluated using Cell Counting Kit-8 (CCK-8), transwell, and flow cytometry assay, respectively. Potential binding sites between miR-432-5p and SORT1 were predicted with TargetScan and validated through dual-luciferase reporter assay and co-transfection experiments. Serum miR-432-5p was decreased, while SORT1 was elevated in CAD patients and ox-LDL-induced HASMCs. miR-432-5p showed a negative correlation with total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), C-reactive protein (CRP), and Gensini score. miR-432-5p and SORT1 effectively distinguished CAD patients from controls based on ROC analysis. miR-432-5p and SORT1 serve as independent risk predictors. Restoration of miR-432-5p reversed ox-LDL-induced increases in HASMC proliferation and migration and restored apoptosis levels. SORT1 was confirmed as a direct target of miR-432-5p, and its upregulation counteracted the protective effects of miR-432-5p on HASMC under ox-LDL exposure. This study suggests that miR-432-5p protects HASMCs and inhibits coronary artery disease progression by targeting SORT1, positioning both miR-432-5p and SORT1 as potential biomarkers for CAD.
近期研究突显了微小RNA（miRNA）在冠状动脉疾病（CAD）中的关键作用。这项回顾性研究调查了CAD患者血清中miR-432-5p的丰度，并探讨了其作用。纳入了252名志愿者。通过qRT-PCR对CAD患者血清以及氧化型低密度脂蛋白（ox-LDL）处理的人动脉平滑肌细胞（HASMCs）中miR-432-5p和sortilin 1（SORT1）的水平进行定量。分别采用Pearson相关性分析、受试者工作特征（ROC）曲线分析和二项逻辑回归分析相关系数、临床诊断性能及危险因素。分别使用细胞计数试剂盒-8（CCK-8）、Transwell小室和流式细胞术检测评估HASMC的增殖、迁移和凋亡。利用TargetScan预测miR-432-5p与SORT1之间的潜在结合位点，并通过双荧光素酶报告基因检测和共转染实验进行验证。CAD患者及ox-LDL诱导的HASMCs中血清miR-432-5p降低，而SORT1升高。miR-432-5p与总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、C反应蛋白（CRP）和Gensini评分呈负相关。基于ROC分析，miR-432-5p和SORT1能有效区分CAD患者与对照组。miR-432-5p和SORT1可作为独立的风险预测指标。miR-432-5p的恢复逆转了ox-LDL诱导的HASMC增殖和迁移增加，并恢复了凋亡水平。SORT1被确认为miR-432-5p的直接靶点，其上调抵消了miR-432-5p在ox-LDL暴露下对HASMCs的保护作用。本研究表明，miR-432-5p通过靶向SORT1保护HASMCs并抑制冠状动脉疾病进展，提示miR-432-5p和SORT1均为CAD的潜在生物标志物。
