| Objective:Acute coronary syndrome(ACS)is the most common cardiovascular emergency.Timely diagnosis of ACS contributes to improved patient outcomes as well as reduced cardiovascular mortality.However,existing diagnostic markers for ACS are flawed,lacking in properties with both high sensitivity and high specificity at the same time.Currently,the gold standard for assessing the severity of coronary artery lesions is the invasive coronary angiography,which is costly and risky.Therefore,safe and efficacious biomarkers,which can be applied in the diagnosis of ACS and the assessment of the severity of coronary artery lesions,are urgently needed in the clinic.Exosomes are lipid bilayer vesicles secreted by cells,which can participate in the pathophysiological process of cardiovascular diseases by carrying miRNA,lncRNA and other biological molecules.They serve as potential tools for the diagnosis and monitoring of cardiovascular diseases.Studies have shown that miR-499,miR-939 and MALAT1 are related to myocardial hypoxia and endothelial function.These molecules can be carried by exosomes.The pathogenesis of ACS is closely related to myocardial hypoxia injury,plaque rupture,endothelial dysfunction and inflammatory reaction.The above evidence suggests that miR-499,miR-939 and MALAT1 may be involved in the occurrence and development of ACS.Currently,the value of plasma exosomal miR-499,miR-939,and MALAT1 in both diagnosis of ACS and the prediction of the severity of coronary artery lesions remains unknown.In this study,the expression levels of plasma exosomal miR-499,miR-939 and MALAT1 in the control group,unstable angina(UA)group and acute myocardial infarction(AMI)group were detected.The feasibility of plasma exosomal miR-499,miR-939 and MALAT1 as biomarkers of UA and AMI were assessed.And we explored whether the expression levels of these three biomarkers had the value of predicting the severity of coronary artery lesions.Methods:62 patients with ACS hospitalized in the department of cardiology of the Second Hospital of Jilin University from December 2019 to December 2020 were enrolled,including 34 patients in AMI group and 28 patients in UA group.Another31 patients who were hospitalized in our department in the same period and confirmed by coronary angiography showing no obvious coronary stenosis were randomly selected as control group.The total RNA of plasma exosomes was extracted by kit,and the expression levels of miR-499,miR-939 and MALAT1 were detected by real-time PCR.Spearman correlation analysis was used to determine the correlation between the expression levels of miR-499,miR-939 and MALAT1 and Gensini score.Receiver operating characteristic curve(ROC)was established to evaluate the predictive values of plasma exosomal miR-499,miR-939 and MALAT1 for AMI and UA.Results:1.There were no significant differences in age,gender,heart rate,systolic blood pressure,diastolic blood pressure,hypertension,diabetes,smoking,body mass index,TC,TG,LDL-C and HDL-C among the three groups(P > 0.05).2.The expression levels of plasma exosomal miR-499,miR-939 and MALAT1 in the control group,UA group and AMI group were detected.The expression level of exosomal miR-499 in AMI group was higher than that in UA group(P < 0.01)and control group(P < 0.001),but there was no significant difference between UA group and control group(P > 0.05).The expression level of exosomal miR-939 in AMI group was lower than that in UA group(P < 0.01)and control group(P < 0.001),and the expression of exosomal miR-939 in UA group was lower than that in control group(P < 0.001).The expression level of exosomal MALAT1 in AMI group was higher than that in UA group(P < 0.05)and control group(P < 0.001),but there was no significant difference between UA group and control group(P > 0.05).3.Spearman correlation revealed that there was a negative correlation between the expression of exosomal miR-939 and Gensini score in AMI and UA groups(r =-0.416,P < 0.05;r =-0.561,P < 0.01).There was no correlation between the expression of exosomal miR-499 and Gensini score in AMI and UA groups(r =0.138,P > 0.05;r = 0.116,P > 0.05).There was no correlation between the expression of exosomal MALAT1 and Gensini score in AMI and UA groups(r =0.259,P > 0.05;r=-0.005,P > 0.05).4.ROC results showed that the area under the ROC curve of plasma exosomal miR-499 expression in the diagnosis of AMI was 0.780(95% CI: 0.677～0.883,P <0.0001),the optimal cut-off value was 1.780,and the sensitivity was 67.7%,the specificity was 83.1%.The area under the ROC curve of plasma exosomal miR-939 expression in the diagnosis of AMI was 0.925(95% CI: 0.865～0.985,P < 0.0001),the optimal cut-off value was 2.010,and the sensitivity was 88.2%,the specificity was 87.1%.The area under the ROC curve of plasma exosomal MALAT1 expression in the diagnosis of AMI was 0.720(95% CI: 0.605～0.835,P < 0.001),the optimal cut-off value was 1.625,and the sensitivity was 64.7%,the specificity was 76.3%.The area under the ROC curve of plasma exosomal miR-939 expression in the diagnosis of UA was 0.783(95% CI: 0.665～0.902,P < 0.001),the optimal cut-off value was 1.583,and the sensitivity was 71.4%,the specificity was 83.9%.Conclusion:1.The expression of miR-499 and MALAT1 in plasma exosomes was up-regulated,while the expression of miR-939 was down-regulated in AMI group.ROC curve suggested that exosomal miR-499,miR-939 and MALAT1 could be used as auxiliary potential biomarkers in the diagnosis of AMI.2.The expression of miR-939 in plasma exosomes was down-regulated in UA group.ROC curve suggested that exosomal miR-939 could be used as an auxiliary potential biomarker in the diagnosis of UA.3.The expression of exosomal miR-939 was negatively correlated with Gensini score in patients with AMI and UA,suggesting that exosomal miR-939 correlated with the severity of coronary artery lesions,which has the potential to predict the severity of coronary artery lesions. |
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