循环miR-155/PDCD4水平与冠状动脉病变严重程度关联研究

Association between circulating miR-155/PDCD4 levels and severity of coronary artery disease

目的探讨冠状动脉粥样硬化性心脏病(冠心病,CAD)患者外周循环血CD4+T细胞miR-155和程序性死亡因子4(PDCD4)基因表达水平变化及其与冠状动脉(冠脉)病变严重程度的关系。方法选取2017年6月至2018年5月于漯河市中心医院心血管内科进行冠状动脉造影术(CAG)并住院接受治疗的CAD患者285例。另外选择非冠心病受试对象50例作为对照组。比较不同亚组CAD患者一般临床资料、CD4+T细胞miR-155和PDCD4mRNA的表达量,采用多因素Logistic回归分析CAD发病的危险因素。采用受试者工作特征(ROC)曲线分析miR-155和PDCD4对重度冠状动脉病变的早期诊断价值。结果与对照组受试者相比,CAD组患者三酰甘油(TG)、尿素氮(BUN)、血清肌酐(SCr)、空腹血糖及CD4+T细胞miR-155、PDCD4mRNA水平均较高,存在统计学差异(P<0.05)。经多因素Logistic回归分析,外周循环血CD4+T细胞miR-155和PDCD4水平、TG水平、空腹血糖水平是影响CAD发生的独立危险因素(P<0.05)。三支病变亚组CAD患者CD4+T细胞miR-155/PDCD4mRNA表达量和Gensini评分明显高于单支病变和双支病变患者(P<0.05)。冠脉重度狭窄亚组CAD患者CD4+T细胞miR-155/PDCD4mRNA表达量和Gensini评分明显高于轻中度狭窄亚组患者(P<0.05)。重度冠脉病变亚组CAD患者CD4+T细胞miR-155/PDCD4mRNA表达量明显高于轻中度病变亚组患者(P<0.05)。经ROC曲线分析,miR-155、PDCD4以及miR-155/PDCD4诊断重度冠脉病变的AUC分别为0.766(95%CI:0.631~0.908)、0.714(95%CI:0.594~0.875)、0.897(95%CI:0.732~0.981)(P<0.05)。结论外周循环血CD4+T细胞miR-155和PDCD4表达水平与冠状动脉病变程度密切相关,可作为诊断重度冠脉病变的参考指标。

Objective To investigate the changes of miR-155 and programmed death factor 4 (PDCD4) gene expression in peripheral blood CD4+ T cells of patients with coronary heart disease (CAD) and its relationship with the severity of coronary artery disease. Methods A total of 285 CAD patients who underwent coronary angiography (CAG) and were hospitalized for treatment in the Department of Cardiology,Luohe Central Hospital from June to May 2018, 2017 were selected. In addition,50 patients with non-coronary heart disease were selected as the control group. The clinical data of different subgroups of CAD patients,the expression of miR-155 and PDCD4 mRNA in CD4+ T cells were compared. Multivariate logistic regression was used to analyze the risk factors of CAD. The receiver operating characteristic (ROC) curve was used to analyze the early diagnostic value of miR-155 and PDCD4 for severe coronary artery disease. Results The levels of triglyceride (TG),blood urea nitrogen (BUN),serum creatinine (SCr),fasting plasma glucose (FPG),CD4+ T lymphocytes miR-155/PDCD4 mRNA in CAD patients were higher than the control subjects (P<0.05). By multivariate Logistic analysis,TG,FPG,miR-155,PDCD4 were the independent risk factors of CAD (P<0.05). The expressions of miR-155/PDCD4 mRNA and Gensini scores in patients with three lesions were higher than the patients with a group of lesions or two lesions (P<0.05). The expressions of miR-155/PDCD4 mRNA and Gensini scores in patients with severe coronary artery stenosis were higher than the patients with mild or moderate coronary artery stenosis (P<0.05). The expressions of miR-155/PDCD4 mRNA in patients with severe coronary artery lesions were higher than the patients with mild or moderate coronary artery lesions (P<0.05). According to the results of ROC curve,AUCs of miR-155,PDCD4 and miR-155/PDCD4 combination were respectively 0.766 (95%CI:0.631~0.908),0.714 (95%CI:0.594~0.875),0.897 (95%CI:0.732~0.981)(P<0.05) Conclusion The CD4+ T lymphocytes miR-155/PDCD4 could be the potential targets of diagnosis and the individual gene therapy for coronary artery disease,as the diagnostic indexes of the severity of coronary artery lesions.