title: Plasma MicroRNAs as sensitive and specific biomarkers of tissue injury.
abstract: BACKGROUND
  MicroRNAs (miRNAs) are endogenous, small noncoding RNAs. Because of their size, abundance, tissue specificity, and relative stability in plasma, miRNAs hold promise as unique accessible biomarkers to monitor tissue injury.
  
  
  METHODS
  We investigated the use of liver-, muscle- and brain-specific miRNAs as circulating biomarkers of tissue injury. We used a highly sensitive quantitative PCR assay to measure specific miRNAs (miR-122, miR-133a, and miR-124) in plasma samples from rats treated with liver or muscle toxicants and from a rat surgical model of stroke.
  
  
  RESULTS
  We observed increases in plasma concentrations of miR-122, miR-133a, and miR-124 corresponding to injuries in liver, muscle, and brain, respectively. miR-122 and miR-133a illustrated specificity for liver and muscle toxicity, respectively, because they were not detectable in the plasma of animals with toxicity to the other organ. This result contrasted with the results for alanine aminotransferase (ALT) and aspartate aminotransferase, which were both increased with either organ toxicity. Furthermore, miR-122 exhibited a diagnostic sensitivity superior to that of ALT when the results were correlated to the liver histopathologic results. The miR-124 concentration increased in the plasma of rats 8 h after surgery to produce brain injury and peaked at 24 h, while the miR-122 and miR-133a concentrations remained at baseline values.
  
  
  CONCLUSIONS
  These results demonstrate that tissue-specific miRNAs may serve as diagnostically sensitive plasma biomarkers of tissue injury.
authors.affiliation: Merck Research Laboratories, Clinical Development Laboratory, Rahway, NJ, USA.
authors.forename: Omar F
authors.initials: OF
authors.lastname: Laterza
authors.forename: Lee
authors.initials: L
authors.lastname: Lim
authors.forename: Philip W
authors.initials: PW
authors.lastname: Garrett-Engele
authors.forename: Katerina
authors.initials: K
authors.lastname: Vlasakova
authors.forename: Nagaraja
authors.initials: N
authors.lastname: Muniappa
authors.forename: Wesley K
authors.initials: WK
authors.lastname: Tanaka
authors.forename: Jason M
authors.initials: JM
authors.lastname: Johnson
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Sina
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Fare
authors.forename: Frank D
authors.initials: FD
authors.lastname: Sistare
authors.forename: Warren E
authors.initials: WE
authors.lastname: Glaab
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D005260:Female; D006335:Heart Injuries / Q000175:diagnosis / Q000235:genetics; D007668:Kidney / Q000293:injuries / Q000473:pathology; D008099:Liver / Q000293:injuries / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D018482:Muscle, Skeletal / Q000293:injuries / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000175:diagnosis / Q000235:genetics; D014947:Wounds and Injuries / Q000175:diagnosis* / Q000235:genetics*
chemical_list: D015415:Biomarkers; D035683:MicroRNAs