Ⅰ.Plasma Microrna Expression Profile Of Patients With Stanford Type A Aortic Dissection Ⅱ.Analysis Of Preoperative Coronary Angiography In Patients With Valvular Heart Disease

Objective:Firstly,identify the serum microRNA(miRNA)expression profile of patients with Stanford type A aortic dissection,especially those who has a history of hypertension.Then investigate the role of a selected panel of miRNAs as potential biomarkers for aortic dissection.Secondly,estimate the positive rate of preoperative coronary angiography(CAG)in valvular heart disease(VHD),and subsequently assess the possible predictive factors for the presence of positive coronary angiography.Methods:1)TaqMan low density array and real-time polymerase chain reaction(RT-qPCR)were used to determine the miRNA expression level of four groups of human serum samples,including normal control(NC,n=15),hypertension control(HC,n=15),Stanford type A aortic dissection comorbidities with hypertension(HAD,n=15)and Stanford type A aortic dissection without hypertension(NHAD,n=15).Then other 67 human serum samples(NC=14,HC=14,HAD=29 and NHAD=10)were used for validation by RT-qPCR.In addition,risk score analysis was performed to evaluate the diagnostic value of the serum miRNA profiling system,which serves as a serum biomarker for Stanford type A aortic dissection.2)With multiple logistic regression analysis,a prognostic index for predicting positive coronary angiography(defined as stenosis of 50%or more of the diameter of the left main and/or left anterior descending coronary artery,or stenosis of 70%or more of the diameter of left circumflex artery and/or right coronary artery)was established by retrospective analysis of the clinical data from 908 patients with preoperative routine coronary angiography for valve replacement.Results:1)Compared with NC group,miR-25 and miR-212 showed significantly down-regulation(-50%of decrease)in HC group(p<0.001),however,both of them were up-regulated more than two-fold in HAD and NHAD groups(p<0.001).MiR-29a and miR-150 were specifically overexpressed in HAD group(miR-29a:>3-fold increase vs NC,HC and NHAD p<0.001;miR-150:>2-fold vs NC,HC and NHAD,p≤0.005).MiR-155 showed more than two-fold increase in HAD and NHAD groups,with the highest expression level in NHAD group(～1.6 folds of HAD).MiR-26b-3p showed a relatively higher expression level in HC group than other groups(～1.5 fold vs.NC,HAD and NHAD,p≤0.001).ROC analysis indicated that miR-25 can serve as an ideal biomarker to distinguish HAD and NHAD from HC patients,respectively(AUC=0.961,95%CI:0.912-1.000,p<0.001;sensitivity:96.4%,specificity;84.2%;AUC=0.926,95%CI:0.845-1.000,p<0.001;sensitivity:90.0%,specificity:89.5%).MiR-150 can also distinguish HAD from NHAD patients,with an 83.9%’s sensitivity and 92.9%’s specificity(AUC=0.908,95%CI:0.823-0.993,p<0.001).MiR-212 can differentiated aortic dissection from other groups of patients,such as HAD and NC(AUC=0.906,95%CI:0.826-0.985,p<0.001;sensitivity:78.8%,specificity:100.0%),HC and HAD(AUC=0.951,95%CI:0.897-1.000,p<0.001;sensitivity:93.9%,specificity:84.2%),HAD and HC+NC(AUC=0.929,95%CI:0.872-0.987,p<0.001;sensitivity:78.8%,specificity:94.6%.Therefore,miR-212 can be served as a reliable serum diagnostic biomarker of aortic dissection.2)Among the 908 valvular heart disease patients,130 patients showed positive CAG.The positive rate of CAG was 14.32%,in which 12.63%(60/475)was female,and 16.17%(70/433)was male.Although a higher positive rate was observed in male patients,there is no statistically significant difference between male and female patients.Multiple logistic regression analysis showed that the three independent risk factors of female with positive CAG are aging(OR=1.129,95%CI:1.079-1.181),hypertension(OR=1.993,95%CI:1.101-3.609)and high LDL-C level(OR=1.613,95%CI:1.099-2.368).The AUC of booth the logistic model and the bootstrap model was 0.782(95%CI:0.722-0.842).In male,the independent risk factors included aging(OR=1.058,95%CI:1.020-1.098),typical angina(OR=11.915,95%CI:3.888-36.510),diabetes mellitus(ORF=2.817,95%CI:1.178-6.733),high LDL-C level(OR=1.1790,95%CI:1.220-2.625)and low HDL-C level(OR=0.294,95%CI:0.116-0.744).Using these independent predictions and NYHA classification,we established a logistic model,with AUC of 0.755(95%CI:0.691-0.819).Conclusions:1)MiR-25 and miR-212 were decreased in the serum of hypertension patients,while these two miRNAs were increased in the serum of Stanford type A aortic dissection patients.MiR-29a and miR-150 were specifically highly expressed in Stanford type A aortic dissection patients,especially in those who have hypertension history.MiR-155 was up-regulated in the serum of Stanford type A aortic dissection patients.MiR-29a,miR-150,miR-155 and miR-212 could be potential serum risk biomarkers of Stanford type A aortic dissection for hypertension patients.Furthermore,miR-150 and miR-29a could be biomarkers of a longer time blood pressure level for Stanford type A aortic patient.2)The positive rate of preoperative CAG was 14.32%,in which 12.63%was female and 16.17%was male.As the high negative rate of routine CAG before valve surgery,it is difficult to achieve high accuracy only by using ordinary clinical data,serum microRNA profile would be potent new diagnostic biomarkers.