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Atherosclerosis-related circulating miRNAs as novel and sensitive predictors for acute myocardial infarction.

ABSTRACT: BACKGROUND: The dysregulated expressions of circulating miRNAs have been detected in various cardiovascular diseases. In our previous experiments, the altered expressions of circulating miRNA-21-5p, miRNA-361-5p and miRNA-519e-5p were confirmed in patients with coronary atherosclerosis by miRNA microarrays. However, the expression levels of these circulating miRNAs in the early phase of acute myocardial infarction (AMI) are still unknown. In the present study, our aims were to examine the expressions of circulating miR-21-5p, miR-361-5p and miR-519e-5p in AMI patients, and assess their clinical applications for diagnosing and monitoring AMI. RESULTS: Two different cohorts were enrolled in this study. The first cohort included 17 AMI patients and 28 healthy volunteers, and the second cohort included 9 AMI patients, 9 ischemic stroke patients, 8 patients with pulmonary embolism, and 12 healthy volunteers. Quantitative real-time PCR and ELISA assays were preformed to detect the concentrations of plasma miRNAs and cardiac troponin I (cTnI), respectively. The results showed that the plasma levels of miR-21-5p and miR-361-5p were significantly increased in AMI patients, whereas the concentration of circulating miR-519e-5p was reduced. Interestingly, the levels of these circulating miRNAs correlated with the concentrations of plasma cTnI. Receiver operating characteristic (ROC) analysis revealed that these three circulating miRNAs had considerable diagnostic accuracy for AMI with high values of area under ROC curve (AUC). Importantly, combining the three miRNAs significantly increased the diagnostic accuracy. Furthermore, cell experiments demonstrated that these plasma miRNAs may originate from injured cardiomyocytes induced by hypoxia. In addition, the levels of all the three circulating miRNAs in ischemic stroke (IS) and pulmonary embolism (PE) were elevated, whereas the decreased level of plasma miR-519e-5p was only detected in AMI. ROC analysis demonstrated that circulating miR-519e-5p may be a useful biomarker for distinguishing AMI from other ischemic diseases. CONCLUSIONS: Circulating miRNAs may be novel and powerful biomarkers for AMI and they could be potential diagnostic tool for AMI.

SUBMITTER: Wang F

PROVIDER: S-EPMC4153586 | biostudies-other | 2014

REPOSITORIES: biostudies-other

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Atherosclerosis-related circulating miRNAs as novel and sensitive predictors for acute myocardial infarction.

Wang Feng F Long Guangwen G Zhao Chunxia C Li Huaping H Chaugai Sandip S Wang Yan Y Chen Chen C Wang Dao Wen DW

PloS one 20140903 9

<h4>Background</h4>The dysregulated expressions of circulating miRNAs have been detected in various cardiovascular diseases. In our previous experiments, the altered expressions of circulating miRNA-21-5p, miRNA-361-5p and miRNA-519e-5p were confirmed in patients with coronary atherosclerosis by miRNA microarrays. However, the expression levels of these circulating miRNAs in the early phase of acute myocardial infarction (AMI) are still unknown. In the present study, our aims were to examine the ...[more]

PMID: 25184815

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Project description:BackgroundAcute myocardial infarction (AMI) is the main clinical cause of death and cardiovascular disease and thus has high rates of morbidity and mortality. The increase in cardiovascular disease with aging is partly the result of vascular endothelial cell senescence and associated vascular dysfunction. This study was performed to identify potential key cellular senescence-related genes (SRGs) as biomarkers for the diagnosis of AMI using bioinformatics.MethodsUsing the CellAge database, we identified cellular SRGs. GSE66360 and GSE48060 for AMI patients and healthy controls and GSE19322 for mice were downloaded from the Gene Expression Omnibus (GEO) database. The GSE66360 dataset was divided into a training set and a validation set. The GSE48060 dataset was used as another validation set. The GSE19322 dataset was used to explore the evolution of the screened diagnostic markers in the dynamic process of AMI. Differentially expressed genes (DEGs) of AMI were identified from the GSE66360 training set. Differentially expressed senescence-related genes (DESRGs) selected from SRGs and DEGs were analyzed using Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and protein-protein interaction (PPI) networks. Hub genes in DESRGs were selected based on degree, and diagnostic genes were further screened by gene expression and receiver operating characteristic (ROC) curve. Finally, a miRNA-gene network of diagnostic genes was constructed and targeted drug prediction was performed.ResultsA total of 520 DEGs were screened from the GSE66360 training set, and 279 SRGs were identified from the CellAge database. The overlapping DEGs and SRGs constituted 14 DESRGs, including 4 senescence suppressor genes and 10 senescence inducible genes. The top 10 hub genes, including FOS, MMP9, CEBPB, CDKN1A, CXCL1, ETS2, BCL6, SGK1, ZFP36, and IGFBP3, were screened. Furthermore, three diagnostic genes were identified: MMP9, ETS2, and BCL6. The ROC analysis showed that the respective area under the curves (AUCs) of MMP9, ETS2, and BCL6 were 0.786, 0.848, and 0.852 in the GSE66360 validation set and 0.708, 0.791, and 0.727 in the GSE48060 dataset. In the GSE19322 dataset, MMP9 (AUC, 0.888) and ETS2 (AUC, 0.929) had very high diagnostic values in the early stage of AMI. Finally, based on these three diagnostic genes, we found that drugs such as acetylcysteine and genistein may be targeted for the treatment of age-related AMI.ConclusionThe results of this study suggest that cellular SRGs might play an important role in AMI. MMP9, ETS2, and BCL6 have potential as specific biomarkers for the early diagnosis of AMI.

Project description:OBJECTIVE:We hypothesized that Displacement Encoding with Stimulated Echoes (DENSE) and feature-tracking derived circumferential strain would provide incremental prognostic value over the extent of infarction for recovery of segmental myocardial function. METHODS:Two hundred and sixty-one patients (mean age 59 years, 73% male) underwent MRI 2 days post-ST elevation myocardial infarction (STEMI) and 241 (92%) underwent repeat imaging 6 months later. The MRI protocol included cine, 2D-cine DENSE, T2 mapping and late enhancement. Wall motion scoring was assessed by 2-blinded observers and adjudicated by a third. (WMS: 1=normal, 2=hypokinetic, 3=akinetic, 4=dyskinetic). WMS improvement was defined as a decrease in WMS???1, and normalization where WMS?=?1 on follow-up. Segmental circumferential strain was derived utilizing DENSE and feature-tracking. A generalized linear mixed model with random effect of subject was constructed and used to account for repeated sampling when investigating predictors of segmental myocardial improvement or normalization RESULTS: At baseline and follow-up, 1416 segments had evaluable data for all parameters. Circumferential strain by DENSE (p?<?0.001) and feature-tracking (p?<?0.001), extent of oedema (p?<?0.001), infarct size (p?<?0.001), and microvascular obstruction (p?<?0.001) were associates of both improvement and normalization of WMS. Circumferential strain provided incremental predictive value even after accounting for infarct size, extent of oedema and microvascular obstruction, for segmental improvement (DENSE: odds ratio, 95% confidence intervals: 1.08 per -1% peak strain, 1.05-1.12, p?<?0.001, feature-tracking: odds ratio, 95% confidence intervals: 1.05 per -1% peak strain, 1.03-1.07, p?<?0.001) and segmental normalization (DENSE: 1.08 per -1% peak strain, 1.04-1.12, p?<?0.001, feature-tracking: 1.06 per -1% peak strain, 1.04-1.08, p?<?0.001). CONCLUSIONS:Circumferential strain provides incremental prognostic value over segmental infarct size in patients post STEMI for predicting segmental improvement or normalization by wall-motion scoring.

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Atherosclerosis-related circulating miRNAs as novel and sensitive predictors for acute myocardial infarction.

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Atherosclerosis-related circulating miRNAs as novel and sensitive predictors for acute myocardial infarction.

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