| Background:Acute myocardium infarction(AMI)is one of the main causes of cardiovascular diseases death,and timely intervention and diagnosis are essential.Exosomes are small vesicles secreted by cells and can participate in the normal physiological and pathophysiological processes of the development of cardiovascular diseases.The contents,such as proteins,lipids,mRNA and miRNA can represent the cell source of exosomes and reflect the state of the source cell,the level of these contents will change under different pathological conditions,and can be used as non-invasive biomarkers for diagnosis.Exosomes can also serve as intercellular communication messengers,send large amounts of proteins,RNAs and lipids to receptor cells,regulate the function of target cells,participate in tissue repair and regeneration after cardiovascular disease injury.The occurrence of acute myocardial infarction is closely related to lipid infiltration,endothelial injury,inflammatory response,plaque rupture,and thrombosis,etc.It has been shown that NEAT1 can promote the expression of inflammatory factors and aggravate the ischemia-reperfusion injury by inhibiting the downstream miRNA,and inflammation can promote the production of matrix metalloproteinases(MMPs)to lead to acute coronary syndrome.It was found that NEAT1 promoted the secretion of MMP-9 in tumor cells to stimulate cell metastasis and invasion;NEAT1 indirectly up-regulated ZEB1 by inhibiting miR-204 to promote epithelial mesenchymal transformation;miR-204 also inhibited the invasion of trophoblast cells by affecting MMP-9.At present,it is unclear whether lncRNA NEAT1 in serum exosomes will promote the expression of MMP-9 through miR-204 to accelerate the process of acute myocardial infarction and the predictive value for myocardial infarction.Objective:In this study,the expression changes of serum exosomal NEAT,miR-204,and MMP-9 in the control,UA and STEMI groups were detected,the differences among three groups were compared,analyzed the correlations of three detection indexes in STEMI and evaluated their predictive values for acute ST-segment elevation myocardial infarction.Methods:From November 2018 to September 2019,47 patients with STEMI and 24 patients with UA,were first time diagnosed in our hospital.The 27 patients in the control group were hospitalized in the same period,and coronary angiography showed no obvious stenosis.The kit was used to extract the RNA from the serum exosomes of the subjects,and the expressions of NEAT1 and miR-204 were detected by qRT-PCR.The serum exosomes were extracted by ultracentrifugation,and the western blot was used to detect MMP-9.Spearman test was used to analyze the correlations among the three.Logistic regression and Receiver-operating characteristic curve(ROC)were used to evaluate the predictions of serum exosomal NEAT1,miR-204,and MMP-9 for acute ST-segment elevation myocardial infarction.Results:(1)We compared the clinical data among the control group,UA group,and STEMI group,and no significant differences in age,gender,diabetes,hypertension,smoking,TG,TC,creatinine,urea nitrogen,or BMI were found among the three groups(p > 0.05).In STEMI group,the level of HDL-C was lower than the control group,and the level of LDL-C was higher than the control group(p < 0.05).The level of CRP was higher in the UA and STEMI groups than in the control group(p < 0.05).(2)The expressions of NEAT1,miR-204,and MMP-9 in the control,UA,and STEMI groups were detected.The expression fold change of NEAT1 was significantly higher in STEMI group than control group(2.95±2.47 vs.1.00±0.75;p < 0.01),At the same time,it was significantly higher than in the UA group(2.95±2.47 vs.1.05±0.85;p < 0.01),but there was no significant difference in the fold change of NEAT1 between the control group and the UA group(1.00±0.75 vs.1.05±0.85;p > 0.05).The expression fold change of miR-204 in the STEMI group was significantly lower than the control group(0.64±0.40 vs.1.00±0.56;p < 0.01),and also lower than the UA group(0.64±0.40 vs.1.11±0.50;p < 0.01),but the control group and UA group were no significant difference in the fold change of miR-204(1.00±0.56 vs.1.11±0.50;p > 0.05).In the STEMI group,the expression fold change of MMP-9 was significantly higher than the control group(3.58±3.17 vs.1.00±0.38;p < 0.01),and also higher than the UA group(3.58±3.17 vs.1.71±0.87;p < 0.05).In addition,there were differences in the fold change of MMP-9 between the control group and the UA group(1.00±0.38 vs.1.71±0.87;p < 0.05).(3)Spearman correlation analysis showed that serum exosomal NEAT1 was positively correlated with MMP-9 in patients with acute ST-segment elevation myocardial infarction(r = 0.320,p < 0.05),but there were no correlations between miR-204 with NEAT1,or MMP-9(r =-0.067,p > 0.05;r =-0.197,p > 0.05,respectively).(4)Logistic regression analysis showed that NEAT1,miR-204,and MMP-9 were independent predictors of acute ST-segment elevation myocardial infarction.ROC was performed to evaluate the predictive values of NEAT1,miR-204,and MMP-9 in serum exosomes for patients with acute ST-segment elevation myocardial infarction.The results showed that the AUC of NEAT1 was 0.822(95% CI: 0.740-0.903,p < 0.01),the optimal cut-off value was 1.84,and the sensitivity and specificity were 63.8% and 88.2%,respectively.In our study,miR-204 expression in serum exosomes decreased in patients with STEMI.We applied 1/miR-204 for ROC analysis.The AUC of 1/miR-204 was 0.743(95% CI: 0.646-0.840,p < 0.01),the optimal cut-off was 0.61,and the sensitivity and specificity were 59.6% and 80.4%,respectively.The AUC of MMP-9 was 0.793(95% CI: 0.702-0.883,p < 0.01),the optimal cut-off value was 1.51,and the sensitivity and specificity were 80.9% and 66.7%,respectively.Because the area under the curve is small,and the specificity and sensitivity are low,serum exosomal NEAT1,miR-204 and MMP-9 are considered as biomarkers for the auxiliary diagnosis of acute ST-segment elevation myocardial infarction.Conclusion:The expressions of NEAT1 and MMP-9 in serum exosomes of patients with acute ST-segment elevation myocardial infarction were up-regulated and positively correlated,miR-204 expression was down-regulated,there were no correlations between miR-204 with NEAT1,or MMP-9.Exosomal NEAT1,miR-204,and MMP-9 displayed potent biomarkers for diagnosis of acute ST-segment elevation myocardial infarction. |
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