title: Refining diagnostic microRNA signatures by whole-miRNome kinetic analysis in acute myocardial infarction.
abstract: BACKGROUND
  Alterations in microRNA (miRNA) expression patterns in whole blood may be useful biomarkers of diverse cardiovascular disorders. We previously reported that miRNAs are significantly dysregulated in acute myocardial infarction (AMI) and applied machine-learning techniques to define miRNA subsets with high diagnostic power for AMI diagnosis. However, the kinetics of the time-dependent sensitivity of these novel miRNA biomarkers remained unknown.
  
  
  METHODS
  To characterize temporal changes in the expressed human miRNAs (miRNome), we performed here the first whole-genome miRNA kinetic study in AMI patients. We measured miRNA expression levels at multiple time points (0, 2, 4, 12, 24 h after initial presentation) in patients with acute ST-elevation myocardial infarction by using microfluidic primer extension arrays and quantitative real-time PCR. As a prerequisite, all patients enrolled had to have cardiac troponin T concentrations <50 ng/L on admission as measured with a high-sensitivity assay.
  
  
  RESULTS
  We found a subset of miRNAs to be significantly dysregulated both at initial presentation and during the course of AMI. Additionally, we identified novel miRNAs that are dysregulated early during myocardial infarction, such as miR-1915 and miR-181c*.
  
  
  CONCLUSIONS
  The present proof-of-concept study provides novel insights into the dynamic changes of the human miRNome during AMI.
authors.affiliation: Department of Internal Medicine, University of Heidelberg, Heidelberg, Germany.
authors.forename: Britta
authors.initials: B
authors.lastname: Vogel
authors.forename: Andreas
authors.initials: A
authors.lastname: Keller
authors.forename: Karen S
authors.initials: KS
authors.lastname: Frese
authors.forename: Wanda
authors.initials: W
authors.lastname: Kloos
authors.forename: Elham
authors.initials: E
authors.lastname: Kayvanpour
authors.forename: Farbod
authors.initials: F
authors.lastname: Sedaghat-Hamedani
authors.forename: Sarah
authors.initials: S
authors.lastname: Hassel
authors.forename: Sabine
authors.initials: S
authors.lastname: Marquart
authors.forename: Markus
authors.initials: M
authors.lastname: Beier
authors.forename: Evangelos
authors.initials: E
authors.lastname: Giannitis
authors.forename: Stefan
authors.initials: S
authors.lastname: Hardt
authors.forename: Hugo A
authors.initials: HA
authors.lastname: Katus
authors.forename: Benjamin
authors.initials: B
authors.lastname: Meder
mesh_terms: D015415:Biomarkers / Q000097:blood; D005260:Female; D023281:Genomics; D006801:Humans; D007700:Kinetics; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000175:diagnosis*; D060888:Real-Time Polymerase Chain Reaction; D019210:Troponin I / Q000097:blood
chemical_list: D015415:Biomarkers; D035683:MicroRNAs; D019210:Troponin I