| Objective:The expression of COX-2 in cardiac tissue of patients with heart failure was increased.Studies found that COX-2 and its metabolites are involved in inflammation,cardiac hypertrophy,ventricular remodeling,and heart failure.We analyzed the gene chip of peripheral blood in patients with heart failure through the website and found that COX-2 was also significantly upregulated in peripheral blood of patients with heart failure.However,whether plasma COX-2 is a biological marker of heart failure and a potential therapeutic target is unclear.MicroRNAs(microRNAs)mainly play a regulatory role by targeting non-coding regions of proteins.microRNAs have significant changes in cardiovascular diseases.They also can be used as biological markers and potential therapeutic targets.In this study,we predicted microRNA-1297 and microRNA-4649 which may be associated with COX-2 by website and detected the expression levels of microRNA-1297,microRNA-4649 and COX-2 in the serum of patients with heart failure.Furthermore,we analyzed their correlations and the sensitivity and specificity of the biology markers for heart failure.In addition,we analyzed the expression of microRNA-1297,microRNA-4649 and COX-2 in hypoxic cardiomyocytes and endothelial cells in vitro.Method:The subjects were 70 patients with heart failure and 37 healthy persons.Patients with heart failure came from November 2016 to March 2017 in the Department of Cardiology,Second Hospital of Jilin University.The expression of plasma COX-2 was detected by ELISA and the expression of microRNA was measured by real-time quantitative polymerase chain reaction(qRT-PCR).The correlation between serum COX-2,microRNA-4649 and microRNA-1297 were assessed by the Spearman correlation test.We also create a receiver operating characteristic curve(ROC curve)to predict the relevant diagnosis of heart failure patients.The area under the ROC curve(AUC)is used to evaluate the predictability of the selected variables and the best cutoff point.Results:1.We found that the expression of COX-2(PTGS2)in peripheral blood of patients with heart failure was elevated by gene websites and it was statistically significant2.The expression of COX-2 and related microRNAs in rat cardiomyocytes(H9c2)and human umbilical vein endothelial cells under hypoxia.The results showed that the expression of COX-2 was up-regulated by 4.37±0.86-fold,microRNA-4649 was down-regulated by 0.643±0.10-fold in H9c2 cells treated with hypoxia for 8 h.The expression of COX-2 was upregulated by 2.3±0.36 fold,microRNA-1297 was downregulated by 0.22±0.10 fold,and microRNA-4649 was downregulated by0.60±0.14 fold in HUVEC cells treated with hypoxia for 8 h.P<0.01,the difference was statistically significant.3.The expression of plasma COX-2 was 20.90±4.52 ng/ml in patients with heart failure,and it was 17.29±4.91 ng/ml in the healthy control group.The expression level of plasma COX-2 was significant elevated in the heart failure group,P < 0.01,the difference was statistically significant.4.The expression of plasma microRNA 4649 was 1.00±0.61 fold in the healthy group and it was 12.58±11.46 fold in the heart failure group.The expression of plasma microRNA-4649 expression was significantly increased in the heart failure group.P<0.01,the difference was statistically significant.5.The expression of plasma microRNA-1297 was 1.00±1.76 fold in the healthy group and it was 0.13±0.29 fold in the heart failure group.The expression of plasma microRNA-4649 expression was significantly reduced in the heart failure group.P<0.01,the difference was statistically significant.6.The correlation analysis between COX-2 and microRNA-4649 in plasma of patients with heart failure showed a positive correlation with R=0.217,p <0.05,the difference was statistically significant.7.The correlation analysis between COX-2 and microRNA-1297 in plasma of patients with heart failure showed a negative correlation with R=0.217,p <0.05,there was no significant difference8.The ROC analysis showed that the AUC of COX-2 was 0.707(95% CI:0.598-0.817;P<0.01),the best cut-off value was 28.5254,the sensitivity was 72.9%and the specificity was 62.2%.Previous studies showed that microRNA-1297 wassignificantly downregulated in heart failure.We chose 1/microRNA-1297 as the ROC curve.The AUC of 1/microRNA-1297 was 0.841(95% CI:0.759-0.923;P<0.01).The best cutoff value is 0.7337,the sensitivity was 80% and the specificity was 78.4%.MicroRNA-4649 was significantly upregulated in heart failure,We chose microRNA-4649 as the ROC curve.The AUC of microRNA-4649 was 0.984(95% CI:0.908-0.988;P<0.01),The best cutoff value was 1.7695,the sensitivity was 92.9%and the specificity was 94.6%.Further logistic regression analysis of the values of cox2 and microRNA-4649 showed that microRNA-4649 has significant sensitivity and specificity for heart failure and it can be a biomarker for the diagnosis of heart failure.Conclusion:1.The expression of COX-2 was significantly upregulated and its associated microRNA was significantly downregulated in hypoxic cardiomyocytes and endothelial cells.2.The expression of COX-2 in plasma of patients with heart failure was significantly up-regulated.The expression of microRNA-4649 was significantly up-regulated and the expression of microRNA-1297 was significantly down-regulated.3.The microRNA-4649 as a biomarker of heart failure exhibits good sensitivity and specificity. |
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