The Relationship Between Plasma Level Of MicroRNA-1 And Coronary Heart Disease Diagnosis Or Prognosis

Objective: Recent studies have revealed that circulating microRNAs(miRNAs) have been proposed as new biomarkers for cardiovascular diseases diagnosis. Some studies have shown up-regulation of plasma miRNA-1 in ischemic myocardium. However,whether miRNA-1 could be a novel biomarker for predicting coronary heart disease(CHD) is unclear. The purpose of present study was to investigate the difference expression of plasma miRNA-1 level between coronary heart disease patients and healthy people. Our study compared the difference of plasma miRNA-1 level between unstable angina pectoris(UAP) and acute myocardial infarction(AMI). We analyzed the relationship among miRNA-1, degree of coronary artery lesions and the clinical examination index. Additionally, present study analyzed the relationship between plasma miRNA-1 and major adverse cardiovascular events(MACE) after percutaneous coronary intervention(PCI), and evaluated the clinical significance and predictive ability of plasma miRNA-1 in CHD patients undergoing PCI.Method: Eighty-seven patients who underwent coronary angiography admitted to Department of Cardiovascular Medicine in Tianjin Chest Hospital during June to October 2014 were analyzed. Peripheral blood of all selected patients was collected,and then extracted the totalRNA. The contents of miRNA-1 were detected by using real-time fluorescence quantitative PCR(q RT-PCR). We collected the basic characteristics of all inclusive patients(eg. smoking, alcohol, Hypertension, Diabetes mellitus), the clinical biochemical index and results of coronary angiography. We evaluated the relationship between miRNA-1 and the clinical index. All CHD patients after PCI were followed up for 1 year and recorded the results of the occurrence of major adverse cardiovascular events(MACE including heart death, non fatal myocardial infarction, angina and target vessel revascularization). We divided the expression levels of plasma miRNA-1 into three groups(Q1 group: low expression level(25%); Q2 group:middle expression level(50%); Q3 group: high expression level(25%)), and analyzed the relationship between plasma miRNA-1 level and MACE after PCI through Kaplan-Meier single factor analysis and survival curve.Result: 1. The expressive level of plasma miRNA-1 in CHD group was significantly higher than that of healthy control group(P<0.05). CHD group was divided into AMI group and UAP group. The level of plasma miRNA-1 of AMI group(7.045±6.360) was up-regulated compared with control group(0.687±0.222) and UAP group(2.773±1.151), and they had statistical difference(P < 0.05). The expression of plasma miRNA-1 in UAP group(2.773±1.151) was significantly higher than control group(0.687±0.222)(P<0.05). 2. The correlation analysis between the plasma miRNA-1 and the clinical examinational index: the expression level of plasma miRNA-1 was positively correlated with cTnI, CK-MB, CK, CRP, sores of Gensini,BNP and LV, and was negatively correlated with LVEF. 3. The ROC(receiver-operating characteristic) curve analysis:(1) ROC curve constructed to compare the relative concentration of plasma miRNA-1 for AMI and non AMI group:Area under the ROC curve(AUC) of miRNA-1 was 0.891(P < 0.05)(95%CI,0.810-0.971), sensitivity was 90.8% and specificity was 93.3%;(2) compare the relative concentration of miRNA-1 for AMI and UAP group: AUC of miRNA-1 was0.780(P<0.05)(95%CI,0.661-0.899), sensitivity was 63.6% and specificity was90.3%;(3) compare the relative concentration of miRNA-1 for UAP and healthy control group: AUC of miRNA-1 was 1.000(P < 0.05)(95%CI, 1.000-1.000),sensitivity was 100% and specificity was 100%; 4. The relationship analysis between the expression level of plasma miRNA-1 and the coronary artery lesions: the expression of plasma miRNA-1 in two vessels and three vessels disease was significantly elevated compared with one vessel disease(7.5248±4.3912 vs2.7023±0.4675;10.0995±7.3954 vs 2.7023±0.4675, P<0.05). the relative expression level of miRNA-1 in 0<Gensini scores?25 group and Gensini scores>25 group was significantly elevated compared healthy control group(P < 0.05). The level of miRNA-1 in Gensini scores>25 group was higher than 0<Gensini scores?25 group(P<0.05). 5. Log-rank single factor analysis of plasma miRNA-1 and MACE after PCI: the total cumulative survival rates had significantly differences in the three group of plasma miRNA-1 levels(x2=16.671,P=0.000); Comparing to the Q1 and Q2 groups, the total cumulative survival rates of the Q3 group had significantly reduced(x2=16.398,P=0.000); Comparing to the Q2 group, the total cumulative survival rates of Q3 group had also significantly reduced(x2=12.053, P=0.001); The total cumulative survival rates had no statistical difference between the Q1 and Q2 group(x2=0.001,P=0.978).Conclusion: The level of plasma miRNA-1 was significantly higher from CHD patients compared with non-CHD group, and the level of miRNA-1 expression was significantly up-regulated in acute myocardial infarction patients. Increased plasma miRNA-1 may be the crucial role in the occurrence and development of the coronary heart disease. Our results demonstrated that plasma miRNA-1 may be potential biomarker for the diagnosis of unstable angina pectoris and acute myocardial infarction, and may be a new diagnosis biomarker in heart failure patients. Plasma miRNA-1 up-regulation may be a potential predictor to appraise the risk of major adverse cardiovascular events in patients after PCI. It is beneficial to improve prognosis of PCI, the quality of life and decrease the mortality in CHD patients through the early alert and intervention therapy in high risk patients.