title: The distribution of circulating microRNA and their relation to coronary disease.
abstract: BACKGROUND
  MicroRNAs (miRNAs) are small RNAs that regulate gene expression by suppressing protein translation and may influence RNA expression. MicroRNAs are detected in extracellular locations such as plasma; however, the extent of miRNA expression in plasma its relation to cardiovascular disease is not clear and many clinical studies have utilized array-based platforms with poor reproducibility.
  
  
  RESULTS
  Initially, to define distribution of miRNA in human blood; whole blood, platelets, mononuclear cells, plasma, and serum from 5 normal individuals were screened for 852 miRNAs using high-throughput micro-fluidic quantitative RT-PCR (qRT-PCR). In total; 609, 448, 658, 147, and 178 miRNAs were found to be expressed in moderate to high levels in whole blood, platelets, mononuclear cells, plasma, and serum, respectively, with some miRNAs uniquely expressed. To determine the cardiovascular relevance of blood miRNA expression, plasma miRNA (n=852) levels were measured in 83 patients presenting for cardiac catheterization. Eight plasma miRNAs were found to have over 2-fold increased expression in patients with significant coronary disease (≥70% stenosis) as compared to those with minimal coronary disease (less than 70% stenosis) or normal coronary arteries. Expression of miR-494, miR-490-3p, and miR-769-3p were found to have significantly different levels of expression. Using a multivariable regression model including cardiovascular risk factors and medications, hsa-miR-769-3p was found to be significantly correlated with the presence of significant coronary atherosclerosis.
  
  
  CONCLUSIONS
  This study utilized a superior high-throughput qRT-PCR based method and found that miRNAs are found to be widely expressed in human blood with differences expressed between cellular and extracellular fractions. Importantly, specific miRNAs from circulating plasma are associated with the presence of significant coronary disease.
authors.affiliation: Department of Medicine, University of Massachusetts Medical School, Massachusetts, 01605, USA.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Freedman
authors.affiliation: Department of Medicine, University of Massachusetts Medical School, Massachusetts, 01605, USA.
authors.forename: Bahadir
authors.initials: B
authors.lastname: Ercan
authors.affiliation: Department of Medicine, University of Massachusetts Medical School, Massachusetts, 01605, USA.
authors.forename: Kristine M
authors.initials: KM
authors.lastname: Morin
authors.affiliation: Department of Biostatistics, School of Public Health, Boston University, Boston, 02118, USA.
authors.forename: Ching-Ti
authors.initials: CT
authors.lastname: Liu
authors.affiliation: Department of Biochemistry, Mersin University, School of Medicine, Mersin, 33343, Turkey.
authors.forename: Lulufer
authors.initials: L
authors.lastname: Tamer
authors.affiliation: Department of Biochemistry, Mersin University, School of Medicine, Mersin, 33343, Turkey.
authors.forename: Lokman
authors.initials: L
authors.lastname: Ayaz
authors.affiliation: Department of Cardiology, Cukurova University, School of Medicine, Adana, 01110, Turkey.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Kanadasi
authors.affiliation: Department of Cardiology, Mersin University, School of Medicine, Mersin, 33343, Turkey.
authors.forename: Dilek
authors.initials: D
authors.lastname: Cicek
authors.affiliation: Department of Cardiology, Mersin University, School of Medicine, Mersin, 33343, Turkey.
authors.forename: Ali Ihsan
authors.initials: AI
authors.lastname: Seyhan
authors.affiliation: Department of Cardiology, Cukurova University, School of Medicine, Adana, 01110, Turkey.
authors.forename: Rabia Eker
authors.initials: RE
authors.lastname: Akilli
authors.affiliation: Department of Oncology, Gaziantep University, School of Medicine, Gazientep, 27310, Turkey.
authors.forename: Celalettin
authors.initials: C
authors.lastname: Camci
authors.affiliation: Department of Physiology, Gaziantep University, School of Medicine, Gazientep, 27310, Turkey.
authors.forename: Beyhan
authors.initials: B
authors.lastname: Cengiz
authors.affiliation: Sahinbey Hospital Central Laboratory, Gaziantep University, Gaziantep, 27310, Turkey.
authors.forename: Serdar
authors.initials: S
authors.lastname: Oztuzcu
authors.affiliation: Department of Medicine, University of Massachusetts Medical School, Massachusetts, 01605, USA.
authors.forename: Kahraman
authors.initials: K
authors.lastname: Tanriverdi