Prospective Study on Circulating MicroRNAs and Risk of Myocardial Infarction
This study sought to explore the association between baseline levels of microRNAs (miRNAs) (1995) and incident myocardial infarction (1995 to 2005) in the Bruneck cohort and determine their cellular origin. Circulating miRNAs are emerging as potential biomarkers. We previously identified an miRNA si...
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| Published in | Journal of the American College of Cardiology Vol. 60; no. 4; pp. 290 - 299 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
New York, NY
Elsevier Inc
24.07.2012
Elsevier Elsevier Limited |
| Subjects | |
| Online Access | Get full text |
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| Abstract | This study sought to explore the association between baseline levels of microRNAs (miRNAs) (1995) and incident myocardial infarction (1995 to 2005) in the Bruneck cohort and determine their cellular origin.
Circulating miRNAs are emerging as potential biomarkers. We previously identified an miRNA signature for type 2 diabetes in the general population.
A total of 19 candidate miRNAs were quantified by real-time polymerase chain reactions in 820 participants.
In multivariable Cox regression analysis, 3 miRNAs were consistently and significantly related to incident myocardial infarction: miR-126 showed a positive association (multivariable hazard ratio: 2.69 [95% confidence interval: 1.45 to 5.01], p = 0.002), whereas miR-223 and miR-197 were inversely associated with disease risk (multivariable hazard ratio: 0.47 [95% confidence interval: 0.29 to 0.75], p = 0.002, and 0.56 [95% confidence interval: 0.32 to 0.96], p = 0.036). To determine their cellular origin, healthy volunteers underwent limb ischemia-reperfusion generated by thigh cuff inflation, and plasma miRNA changes were analyzed at baseline, 10 min, 1 h, 5 h, 2 days, and 7 days. Computational analysis using the temporal clustering by affinity propagation algorithm identified 6 distinct miRNA clusters. One cluster included all miRNAs associated with the risk of future myocardial infarction. It was characterized by early (1 h) and sustained activation (7 days) post–ischemia-reperfusion injury and consisted of miRNAs predominantly expressed in platelets.
In subjects with subsequent myocardial infarction, differential co-expression patterns of circulating miRNAs occur around endothelium-enriched miR-126, with platelets being a major contributor to this miRNA signature. |
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| AbstractList | ObjectivesThis study sought to explore the association between baseline levels of microRNAs (miRNAs) (1995) and incident myocardial infarction (1995 to 2005) in the Bruneck cohort and determine their cellular origin. BackgroundCirculating miRNAs are emerging as potential biomarkers. We previously identified an miRNA signature for type 2 diabetes in the general population. MethodsA total of 19 candidate miRNAs were quantified by real-time polymerase chain reactions in 820 participants. ResultsIn multivariable Cox regression analysis, 3 miRNAs were consistently and significantly related to incident myocardial infarction: miR-126 showed a positive association (multivariable hazard ratio: 2.69 [95% confidence interval: 1.45 to 5.01], p = 0.002), whereas miR-223 and miR-197 were inversely associated with disease risk (multivariable hazard ratio: 0.47 [95% confidence interval: 0.29 to 0.75], p = 0.002, and 0.56 [95% confidence interval: 0.32 to 0.96], p = 0.036). To determine their cellular origin, healthy volunteers underwent limb ischemia-reperfusion generated by thigh cuff inflation, and plasma miRNA changes were analyzed at baseline, 10 min, 1 h, 5 h, 2 days, and 7 days. Computational analysis using the temporal clustering by affinity propagation algorithm identified 6 distinct miRNA clusters. One cluster included all miRNAs associated with the risk of future myocardial infarction. It was characterized by early (1 h) and sustained activation (7 days) post–ischemia-reperfusion injury and consisted of miRNAs predominantly expressed in platelets. ConclusionsIn subjects with subsequent myocardial infarction, differential co-expression patterns of circulating miRNAs occur around endothelium-enriched miR-126, with platelets being a major contributor to this miRNA signature. Objectives This study sought to explore the association between baseline levels of microRNAs (miRNAs) (1995) and incident myocardial infarction (1995 to 2005) in the Bruneck cohort and determine their cellular origin. Background Circulating miRNAs are emerging as potential biomarkers. We previously identified an miRNA signature for type 2 diabetes in the general population. Methods A total of 19 candidate miRNAs were quantified by real-time polymerase chain reactions in 820 participants. Results In multivariable Cox regression analysis, 3 miRNAs were consistently and significantly related to incident myocardial infarction: miR-126 showed a positive association (multivariable hazard ratio: 2.69 [95% confidence interval: 1.45 to 5.01], p = 0.002), whereas miR-223 and miR-197 were inversely associated with disease risk (multivariable hazard ratio: 0.47 [95% confidence interval: 0.29 to 0.75], p = 0.002, and 0.56 [95% confidence interval: 0.32 to 0.96], p = 0.036). To determine their cellular origin, healthy volunteers underwent limb ischemia-reperfusion generated by thigh cuff inflation, and plasma miRNA changes were analyzed at baseline, 10 min, 1 h, 5 h, 2 days, and 7 days. Computational analysis using the temporal clustering by affinity propagation algorithm identified 6 distinct miRNA clusters. One cluster included all miRNAs associated with the risk of future myocardial infarction. It was characterized by early (1 h) and sustained activation (7 days) post-ischemia-reperfusion injury and consisted of miRNAs predominantly expressed in platelets. Conclusions In subjects with subsequent myocardial infarction, differential co-expression patterns of circulating miRNAs occur around endothelium-enriched miR-126, with platelets being a major contributor to this miRNA signature. This study sought to explore the association between baseline levels of microRNAs (miRNAs) (1995) and incident myocardial infarction (1995 to 2005) in the Bruneck cohort and determine their cellular origin.OBJECTIVESThis study sought to explore the association between baseline levels of microRNAs (miRNAs) (1995) and incident myocardial infarction (1995 to 2005) in the Bruneck cohort and determine their cellular origin.Circulating miRNAs are emerging as potential biomarkers. We previously identified an miRNA signature for type 2 diabetes in the general population.BACKGROUNDCirculating miRNAs are emerging as potential biomarkers. We previously identified an miRNA signature for type 2 diabetes in the general population.A total of 19 candidate miRNAs were quantified by real-time polymerase chain reactions in 820 participants.METHODSA total of 19 candidate miRNAs were quantified by real-time polymerase chain reactions in 820 participants.In multivariable Cox regression analysis, 3 miRNAs were consistently and significantly related to incident myocardial infarction: miR-126 showed a positive association (multivariable hazard ratio: 2.69 [95% confidence interval: 1.45 to 5.01], p = 0.002), whereas miR-223 and miR-197 were inversely associated with disease risk (multivariable hazard ratio: 0.47 [95% confidence interval: 0.29 to 0.75], p = 0.002, and 0.56 [95% confidence interval: 0.32 to 0.96], p = 0.036). To determine their cellular origin, healthy volunteers underwent limb ischemia-reperfusion generated by thigh cuff inflation, and plasma miRNA changes were analyzed at baseline, 10 min, 1 h, 5 h, 2 days, and 7 days. Computational analysis using the temporal clustering by affinity propagation algorithm identified 6 distinct miRNA clusters. One cluster included all miRNAs associated with the risk of future myocardial infarction. It was characterized by early (1 h) and sustained activation (7 days) post-ischemia-reperfusion injury and consisted of miRNAs predominantly expressed in platelets.RESULTSIn multivariable Cox regression analysis, 3 miRNAs were consistently and significantly related to incident myocardial infarction: miR-126 showed a positive association (multivariable hazard ratio: 2.69 [95% confidence interval: 1.45 to 5.01], p = 0.002), whereas miR-223 and miR-197 were inversely associated with disease risk (multivariable hazard ratio: 0.47 [95% confidence interval: 0.29 to 0.75], p = 0.002, and 0.56 [95% confidence interval: 0.32 to 0.96], p = 0.036). To determine their cellular origin, healthy volunteers underwent limb ischemia-reperfusion generated by thigh cuff inflation, and plasma miRNA changes were analyzed at baseline, 10 min, 1 h, 5 h, 2 days, and 7 days. Computational analysis using the temporal clustering by affinity propagation algorithm identified 6 distinct miRNA clusters. One cluster included all miRNAs associated with the risk of future myocardial infarction. It was characterized by early (1 h) and sustained activation (7 days) post-ischemia-reperfusion injury and consisted of miRNAs predominantly expressed in platelets.In subjects with subsequent myocardial infarction, differential co-expression patterns of circulating miRNAs occur around endothelium-enriched miR-126, with platelets being a major contributor to this miRNA signature.CONCLUSIONSIn subjects with subsequent myocardial infarction, differential co-expression patterns of circulating miRNAs occur around endothelium-enriched miR-126, with platelets being a major contributor to this miRNA signature. This study sought to explore the association between baseline levels of microRNAs (miRNAs) (1995) and incident myocardial infarction (1995 to 2005) in the Bruneck cohort and determine their cellular origin. Circulating miRNAs are emerging as potential biomarkers. We previously identified an miRNA signature for type 2 diabetes in the general population. A total of 19 candidate miRNAs were quantified by real-time polymerase chain reactions in 820 participants. In multivariable Cox regression analysis, 3 miRNAs were consistently and significantly related to incident myocardial infarction: miR-126 showed a positive association (multivariable hazard ratio: 2.69 [95% confidence interval: 1.45 to 5.01], p = 0.002), whereas miR-223 and miR-197 were inversely associated with disease risk (multivariable hazard ratio: 0.47 [95% confidence interval: 0.29 to 0.75], p = 0.002, and 0.56 [95% confidence interval: 0.32 to 0.96], p = 0.036). To determine their cellular origin, healthy volunteers underwent limb ischemia-reperfusion generated by thigh cuff inflation, and plasma miRNA changes were analyzed at baseline, 10 min, 1 h, 5 h, 2 days, and 7 days. Computational analysis using the temporal clustering by affinity propagation algorithm identified 6 distinct miRNA clusters. One cluster included all miRNAs associated with the risk of future myocardial infarction. It was characterized by early (1 h) and sustained activation (7 days) post-ischemia-reperfusion injury and consisted of miRNAs predominantly expressed in platelets. In subjects with subsequent myocardial infarction, differential co-expression patterns of circulating miRNAs occur around endothelium-enriched miR-126, with platelets being a major contributor to this miRNA signature. |
| Author | Kiechl, Stefan Boulanger, Chantal M. Schett, Georg Weger, Siegfried Renard, Jean-Marie Prokopi, Marianna Drozdov, Ignat Mayr, Manuel Chowienczyk, Philip J. Zampetaki, Anna Willeit, Peter Mayr, Agnes Willeit, Johann Tilling, Lindsey Shah, Ajay |
| Author_xml | – sequence: 1 givenname: Anna surname: Zampetaki fullname: Zampetaki, Anna organization: King's British Heart Foundation Centre, King's College London, London, United Kingdom – sequence: 2 givenname: Peter surname: Willeit fullname: Willeit, Peter organization: Department of Neurology, Medical University Innsbruck, Innsbruck, Austria – sequence: 3 givenname: Lindsey surname: Tilling fullname: Tilling, Lindsey organization: King's British Heart Foundation Centre, King's College London, London, United Kingdom – sequence: 4 givenname: Ignat surname: Drozdov fullname: Drozdov, Ignat organization: King's British Heart Foundation Centre, King's College London, London, United Kingdom – sequence: 5 givenname: Marianna surname: Prokopi fullname: Prokopi, Marianna organization: King's British Heart Foundation Centre, King's College London, London, United Kingdom – sequence: 6 givenname: Jean-Marie surname: Renard fullname: Renard, Jean-Marie organization: Paris Centre de Recherche Cardiovasculaire à l'HEGP, INSERM U970, Paris, France – sequence: 7 givenname: Agnes surname: Mayr fullname: Mayr, Agnes organization: Department of Laboratory Medicine, Bruneck Hospital, Bruneck, Italy – sequence: 8 givenname: Siegfried surname: Weger fullname: Weger, Siegfried organization: Department of Internal Medicine, Bruneck Hospital, Bruneck, Italy – sequence: 9 givenname: Georg surname: Schett fullname: Schett, Georg organization: Department of Internal Medicine III and Institute for Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany – sequence: 10 givenname: Ajay surname: Shah fullname: Shah, Ajay organization: King's British Heart Foundation Centre, King's College London, London, United Kingdom – sequence: 11 givenname: Chantal M. surname: Boulanger fullname: Boulanger, Chantal M. organization: Paris Centre de Recherche Cardiovasculaire à l'HEGP, INSERM U970, Paris, France – sequence: 12 givenname: Johann surname: Willeit fullname: Willeit, Johann organization: Department of Neurology, Medical University Innsbruck, Innsbruck, Austria – sequence: 13 givenname: Philip J. surname: Chowienczyk fullname: Chowienczyk, Philip J. organization: King's British Heart Foundation Centre, King's College London, London, United Kingdom – sequence: 14 givenname: Stefan surname: Kiechl fullname: Kiechl, Stefan organization: Department of Neurology, Medical University Innsbruck, Innsbruck, Austria – sequence: 15 givenname: Manuel surname: Mayr fullname: Mayr, Manuel email: manuel.mayr@kcl.ac.uk organization: King's British Heart Foundation Centre, King's College London, London, United Kingdom |
| BackLink | http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26181270$$DView record in Pascal Francis https://www.ncbi.nlm.nih.gov/pubmed/22813605$$D View this record in MEDLINE/PubMed |
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| Keywords | endothelium MP myocardial infarction biomarker I/R platelets Ct PMP microRNA miRNA qPCR AIC MI cycle threshold quantitative polymerase chain reaction Akaike information criterion ischemia-reperfusion platelet-derived microparticle microparticle Myocardial infarction Prospective Risk factor Cardiovascular disease Risk Circulatory system Cardiology Coronary heart disease Myocardial disease |
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| Snippet | This study sought to explore the association between baseline levels of microRNAs (miRNAs) (1995) and incident myocardial infarction (1995 to 2005) in the... ObjectivesThis study sought to explore the association between baseline levels of microRNAs (miRNAs) (1995) and incident myocardial infarction (1995 to 2005)... Objectives This study sought to explore the association between baseline levels of microRNAs (miRNAs) (1995) and incident myocardial infarction (1995 to 2005)... |
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| SubjectTerms | Adult Aged Biological and medical sciences biomarker Biomarkers Biomarkers - blood Blood platelets Blood Platelets - metabolism Cardiology Cardiology. Vascular system Cardiovascular Cardiovascular disease Case-Control Studies Cohort Studies Confidence intervals Coronary heart disease Diabetes Diabetes Mellitus, Type 2 - blood Diabetes Mellitus, Type 2 - genetics endothelium Female Gene expression Glucose Heart Heart attacks Humans Italy Male Medical sciences microRNA MicroRNAs MicroRNAs - blood MicroRNAs - genetics Middle Aged myocardial infarction Myocardial Infarction - blood Myocardial Infarction - genetics Myocarditis. Cardiomyopathies Plasma platelets Population Proportional Hazards Models Prospective Studies Real-Time Polymerase Chain Reaction Reference Values Reperfusion Injury - blood Reperfusion Injury - genetics Risk Assessment Studies Thigh - blood supply |
| Title | Prospective Study on Circulating MicroRNAs and Risk of Myocardial Infarction |
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