外周血环状RNA circDLGAP4在冠心病中保护的作用

The possible protective role of circDLGAP4 from peripheral blood in coronary heart disease

目的探讨外周血环状RNA circDLGAP4在冠心病中的表达水平及临床意义。方法采用RT-qPCR法检测142例冠心病(CAD)患者和169例对照人群外周血circDLGAP4的表达水平;利用Logistic回归、Spearman相关以及多元线性回归模型分析circDLGAP4与冠心病之间的联系;应用氧化低密度脂蛋白(ox-LDL)处理人单核巨噬细胞,构建动脉粥样硬化泡沫细胞模型,检测不同时间段circDLGAP4表达变化。结果与对照组相比,CAD患者外周血中circDLGAP4的表达水平明显降低(P=0.019); circDLGAP4的相对表达量2-ΔCt每增加1个单位,CAD发病风险降低41.6%(调整后OR=0.584,95%CI:0.394～0.866,P=0.007),且与糖尿病史呈负相关(β=-0.182,P=0.030);在单核巨噬细胞泡沫化进程中,随ox-LDL处理时间增加,circDLGAP4表达水平逐渐降低。结论在冠心病患者外周血白细胞以及单核巨噬细胞泡沫化进程中,circDLGAP4的表达水平明显降低,并与糖尿病发病史呈负相关,可能作为保护因素在冠心病的病理生理进程中发挥作用。

Objective To investigate the expression and clinical significance of circDLGAP4 from peripheral blood in coronary heart disease(CAD).Methods The relative expression level of circDLGAP4 in peripheral blood leukocytes(PBLs)from 142 CAD patients and 169 healthy controls were detected by real-time PCR.Logistic regression,Spearman correlation and multivariate regression analysis were used to investigate the correlation of circDLGAP4 with CAD.THP-1 macrophages were treated with oxidized low density lipoprotein(ox-LDL)to construct an atherosclerotic foam cell model.The levels of circDLGAP4 mRNA were detected at different time points.Results The mRNA expression of circDLGAP4 in PBLs of CAD patients was significantly decreased compared with controls(P=0.019).With increased unit(2-ΔCt)of circDLGAP4 expression,the risk of CAD occurrence reduced by 41.6%(adjusted OR=0.584,95%CI:0.394-0.866,P=0.007).The expression of circDLGAP4 was negatively correlated with T2 DM history(β=-0.182,P=0.030).The level of circDLGAP4 in ox-LDL-treated THP-1 macrophages was decreased in a time-dependent manner.Conclusion The expression of circDLGAP4 was significantly decreased in PBLs of CAD patients and THP-1 macrophages-derived foam cells,and might be a protective factor in the pathophysiology of CAD.