Study Of Exosomal MiR-22,miR-423 And MiR-146a In Peripheral Plasma Of Patients With Acute Coronary Syndrome

Background:Acute coronary syndrome（ACS）is one of the most fatal cardiovascular diseases.The pathological process of acute coronary syndrome is often accompanied by myocardial cell death,which will lead to the decline of cardiac function and ventricular remodeling,and ultimately affect the treatment effect and prognosis of patients with acute coronary syndrome.According to the degree of lesion,acute coronary syndrome is divided into unstable angina（UA）and acute myocardial infarction（AMI）.Apoptosis is one of the main ways of cardiomyocyte death.Early detection and intervention of cardiomyocyte apoptosis is of great significance for the treatment of acute coronary syndrome,the prevention of heart failure and ventricular remodeling.Exosomes are vesicles with lipid bilayer structure.As a natural carrier,exosomes can carry proteins,micro RNAs,lipids and other substances for information transmission between cells and tissues.Micro RNA is an endogenous non-coding RNA,which regulates the expression of target genes by combining with the 3’untranslated region（3’-UTR）of messenger RNA,and then affects cell function.Exsomal miR-22,miR-423 and miR-146 a are involved in regulating ischemia-induced apoptosis of myocardial cells,but their expression levels in peripheral blood of ACS patients and their clinical significance remain unclear.Objective:In this study,the expression changes of exosome miR-22,miR-423 and miR-146 a in plasma of patients in different groups were analyzed by detecting the expression levels of miR-22,miR-423 and miR-146 a in peripheral plasma of patients in control group,unstable angina group（UA group）and acute myocardial infarction group（AMI group）.as well as whether they can be as additional biomarkers for ACS and AMI.Method:In this study,384 inpatients hospitalized in the Hospital of Jilin University from March to December 2021 were randomly selected as the research objects.According to the inclusion criteria and exclusion criteria,93 inpatients were finally selected into the study,including 62 cases in the ACS group（30 cases in the AMI group,32 cases in the UA group）and 31 cases in the control group.General clinical data of the patients were collected,5ml of venous blood was collected from the patients and the plasma was centrifugated for collection.Total RNA in plasma exosomes was extracted with exo RNeasy kit and the expression levels of miR-22,miR-423 and miR-146 a in plasma exosomes of each group were detected with real-time polymerase chain reaction technology.SPSS 23.0 statistical software was used for statistical analysis of the experimental data.ROC curves were used to evaluate the predictive ability of miR-22,miR-423 and miR-146 a in plasma exosomes for ACS and AMI.Results:1.The expressions level of exosomal miR-22,miR-423 and miR-146 a in plasma of patients in the ACS group were significantly up-regulated compared with the control group（p < 0.01,respectively）,ACS subgroup analysis showed that the expression level of exosomal miR-22 in plasma of patients in the AMI group was significantly up-regulated compared with UA group（p < 0.05）,but expression level of miR-423 and miR-146 a showed no significant difference.2.Prediction levels of plasma exosomal miR-22,miR-146 a and miR-423 for AMI: AUC of mi-22 was 0.860（95%CI: 0.7888-0.932;p < 0.01）,the optimal critical value was 7.205,the sensitivity was 100%,and the specificity was 66.7%.The AUC of miR-423 was 0.692（95% CI: 0.580-0.804;p < 0.01）,the optimal critical value was 1.545,the sensitivity was 86.7%,the specificity was 47.6%;The AUC of miR-146 was 0.849（95%CI: 0.773-0.924;p < 0.01）,the optimal critical value was21.23,the sensitivity was 90.0%,the specificity was 73.0%.3.The predictive levels of plasma exosomes miR-22,miR-146 a and miR-423 on ACS: the AUC of miR-22 was 0.947（95%CI: 0.897-0.997;p < 0.01）,the optimal critical value was 2.27,the sensitivity was 95.2%,the specificity was 87.1%;The AUC of miR-423 was 0.895（95% CI: 0.829-0.960;p < 0.01）,the optimal critical value was 1.545,the sensitivity was 87.1%,the specificity was 83.9%;The AUC of miR-146 was 0.987（95%CI: 0.971-1.000;p < 0.01）,the optimal critical value was2.225,the sensitivity was 98.4%,and the specificity was 90.3%.Conclusions:1.The expression levels of plasma exosomal miR-22,miR-423 and miR-146 a in patients with ACS were significantly up-regulated.The expression level of plasma exosomal miR-22 in patients with AMI was significantly higher than that in patients with UA.2.Exosomal miR-22,miR-423 and miR-146 a can be as additional biomarkers for ACS and AMI.