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

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. How...

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Veröffentlicht in:PloS one 2014-09, Vol.9 (9), p.e105734
Hauptverfasser: Wang, Feng, Long, Guangwen, Zhao, Chunxia, Li, Huaping, Chaugai, Sandip, Wang, Yan, Chen, Chen, Wang, Dao Wen
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container_start_page e105734
container_title PloS one
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creator Wang, Feng
Long, Guangwen
Zhao, Chunxia
Li, Huaping
Chaugai, Sandip
Wang, Yan
Chen, Chen
Wang, Dao Wen
description 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. 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. Circulating miRNAs may be novel and powerful biomarkers for AMI and they could be potential diagnostic tool for AMI.
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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. 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. Circulating miRNAs may be novel and powerful biomarkers for AMI and they could be potential diagnostic tool for AMI.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0105734</identifier><identifier>PMID: 25184815</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Aged ; Anticoagulants ; Area Under Curve ; Arteriosclerosis ; Atherosclerosis ; Bioindicators ; Biomarkers ; Biomarkers - blood ; Brain Ischemia - blood ; Brain Ischemia - diagnosis ; Brain Ischemia - genetics ; Calcium-binding protein ; Cardiomyocytes ; Cardiovascular disease ; Cardiovascular diseases ; Case-Control Studies ; Cell adhesion &amp; migration ; Cell Hypoxia ; Cerebral infarction ; Diagnostic software ; Diagnostic systems ; Electrocardiography ; Embolism ; Embolisms ; Enzyme-linked immunosorbent assay ; Female ; Gene expression ; Heart attacks ; Heart diseases ; Hospitals ; Humans ; Hypertension ; Hypoxia ; Infarction ; Internal medicine ; Ischemia ; Kinases ; Male ; Medicine ; Medicine and Health Sciences ; MicroRNAs ; MicroRNAs - blood ; MicroRNAs - genetics ; Middle Aged ; miRNA ; Mortality ; Myocardial infarction ; Myocardial Infarction - blood ; Myocardial Infarction - diagnosis ; Myocardial Infarction - genetics ; Myocytes, Cardiac - metabolism ; Myocytes, Cardiac - pathology ; Patients ; Plasma ; Plasma levels ; Prostate cancer ; Pulmonary Embolism - blood ; Pulmonary Embolism - diagnosis ; Pulmonary Embolism - genetics ; ROC Curve ; Science ; Stroke ; Stroke - blood ; Stroke - diagnosis ; Stroke - genetics ; Therapeutic applications ; Troponin ; Troponin I ; Troponin I - blood ; Troponin I - genetics</subject><ispartof>PloS one, 2014-09, Vol.9 (9), p.e105734</ispartof><rights>2014 Wang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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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. Circulating miRNAs may be novel and powerful biomarkers for AMI and they could be potential diagnostic tool for AMI.</description><subject>Adult</subject><subject>Aged</subject><subject>Anticoagulants</subject><subject>Area Under Curve</subject><subject>Arteriosclerosis</subject><subject>Atherosclerosis</subject><subject>Bioindicators</subject><subject>Biomarkers</subject><subject>Biomarkers - blood</subject><subject>Brain Ischemia - blood</subject><subject>Brain Ischemia - diagnosis</subject><subject>Brain Ischemia - genetics</subject><subject>Calcium-binding protein</subject><subject>Cardiomyocytes</subject><subject>Cardiovascular disease</subject><subject>Cardiovascular diseases</subject><subject>Case-Control Studies</subject><subject>Cell adhesion &amp; migration</subject><subject>Cell Hypoxia</subject><subject>Cerebral infarction</subject><subject>Diagnostic software</subject><subject>Diagnostic systems</subject><subject>Electrocardiography</subject><subject>Embolism</subject><subject>Embolisms</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Female</subject><subject>Gene expression</subject><subject>Heart attacks</subject><subject>Heart diseases</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Hypertension</subject><subject>Hypoxia</subject><subject>Infarction</subject><subject>Internal medicine</subject><subject>Ischemia</subject><subject>Kinases</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>MicroRNAs</subject><subject>MicroRNAs - blood</subject><subject>MicroRNAs - genetics</subject><subject>Middle Aged</subject><subject>miRNA</subject><subject>Mortality</subject><subject>Myocardial infarction</subject><subject>Myocardial Infarction - blood</subject><subject>Myocardial Infarction - diagnosis</subject><subject>Myocardial Infarction - genetics</subject><subject>Myocytes, Cardiac - metabolism</subject><subject>Myocytes, Cardiac - pathology</subject><subject>Patients</subject><subject>Plasma</subject><subject>Plasma levels</subject><subject>Prostate cancer</subject><subject>Pulmonary Embolism - blood</subject><subject>Pulmonary Embolism - diagnosis</subject><subject>Pulmonary Embolism - genetics</subject><subject>ROC Curve</subject><subject>Science</subject><subject>Stroke</subject><subject>Stroke - blood</subject><subject>Stroke - diagnosis</subject><subject>Stroke - genetics</subject><subject>Therapeutic applications</subject><subject>Troponin</subject><subject>Troponin I</subject><subject>Troponin I - blood</subject><subject>Troponin I - 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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. 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. Circulating miRNAs may be novel and powerful biomarkers for AMI and they could be potential diagnostic tool for AMI.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25184815</pmid><doi>10.1371/journal.pone.0105734</doi><oa>free_for_read</oa></addata></record>
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source MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS)
subjects Adult
Aged
Anticoagulants
Area Under Curve
Arteriosclerosis
Atherosclerosis
Bioindicators
Biomarkers
Biomarkers - blood
Brain Ischemia - blood
Brain Ischemia - diagnosis
Brain Ischemia - genetics
Calcium-binding protein
Cardiomyocytes
Cardiovascular disease
Cardiovascular diseases
Case-Control Studies
Cell adhesion & migration
Cell Hypoxia
Cerebral infarction
Diagnostic software
Diagnostic systems
Electrocardiography
Embolism
Embolisms
Enzyme-linked immunosorbent assay
Female
Gene expression
Heart attacks
Heart diseases
Hospitals
Humans
Hypertension
Hypoxia
Infarction
Internal medicine
Ischemia
Kinases
Male
Medicine
Medicine and Health Sciences
MicroRNAs
MicroRNAs - blood
MicroRNAs - genetics
Middle Aged
miRNA
Mortality
Myocardial infarction
Myocardial Infarction - blood
Myocardial Infarction - diagnosis
Myocardial Infarction - genetics
Myocytes, Cardiac - metabolism
Myocytes, Cardiac - pathology
Patients
Plasma
Plasma levels
Prostate cancer
Pulmonary Embolism - blood
Pulmonary Embolism - diagnosis
Pulmonary Embolism - genetics
ROC Curve
Science
Stroke
Stroke - blood
Stroke - diagnosis
Stroke - genetics
Therapeutic applications
Troponin
Troponin I
Troponin I - blood
Troponin I - genetics
title Atherosclerosis-related circulating miRNAs as novel and sensitive predictors for acute myocardial infarction
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