Expression of miR-378a-3p in Peripheral Blood of Patients with Acute Coronary Syndrome and its Diagnostic Value
Objective:To investigate the expression of miR-378a-3p in peripheral blood of patients with acute coronary syndrome(ACS)and its diagnostic value.Methods:Three sera each from patients with acute coronary syndrome(ACS)and healthy individuals(control)were collected and screened by gene microarray to find the most significant differential expression of miR-378a-3p.The correlation between miR-378a-3p and myocardial ischemia was analyzed using network pharmacology.A mouse myocardial ischemia reperfusion(IR)model was constructed and divided into sham operation,I/R 1 h,I/R 3 h,I/R 6 h,and I/R 12 h groups according to the time of ischemia and reperfusion,and the miR-378a-3p expression level in peripheral blood as well as the concentration level of cardiac muscle troponin T(cTnT)were detected.Patients with ACS(101 cases)and the same period of healthy physical examination population(49 cases)were collected and real-time quantitative PCR was performed to detect the expression of miR-378a-3p in patients with ACS.The diagnostic efficacy of miR-378a-3p for the diagnosis of ACS was analyzed by using the receiver operating characteristic curve(ROC),and the risk assessment of ACS was performed.Results:Gene microarray results showed that miR-378a-3p expression was elevated in the peripheral blood of patients with ACS.Network pharmacological analysis suggested that miR-378a-3p and myocardial ischemia share common targets and that miR-378a-3p may intervene in myocardial ischemia through apoptosis and angiogenic pathways,which may be used as a marker for myocardial ischemia.Animal experiments demonstrated that miR-378a-3p expression was gradually up-regulated with the duration of myocardial ischemia,and the expression was significantly increased at 6 h.Moreover,the expression level of miR-378a-3p appeared to be higher in myocardial ischemia at an earlier time than that of cTnT.Clinical data analysis showed that miR-378a-3p in the serum of patients with ACS could be significantly elevated within a short period of time after the clinical symptoms of ACS compared with healthy controls.When miR-378a-3p was used as a specific diagnostic indicator for ACS,the area under the curve(AUC)was 0.8476(95％confidence interval 0.7749-0.9204,P＜0.001),the Yoden index was 0.6981,and the sensitivity and specificity of miR-378a-3p for diagnosing ACS were 0.214 adopted as the cut-off value,respectively were 86.14％and 83.76％.Further studies showed that during the transformation of ischemia,depending on the disease classification,the results showed different trends of miR-378a-3p expression.miR-378a-3p was significantly upregulated in both the unstable angina(UA)and myocardial infarction(MI)groups(P＜0.001),and compared with MI,the upregulation of miR-378a-3p expression in peripheral blood of patients with UA was more significantly(P＜0.05),suggesting a better value in diagnosis and judgment of ACS classification.Conclusion:Elevated miR-378a-3p expression in peripheral blood of patients with ACS is an independent risk factor for the development of ACS,and early detection of miR-378a-3p can help predict the development of ACS.
Acute coronary syndromePeripheral bloodmiR-378a-3pDiagnostic value
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