title: Reduced microRNA-150 is associated with poor survival in pulmonary arterial hypertension.
abstract: BACKGROUND
  MicroRNAs (miRNAs or miRs) are implicated in the pathogenesis of various cardiovascular diseases, including pulmonary arterial hypertension (PAH).
  
  
  OBJECTIVE
  We sought to measure changes in plasma levels of miRNAs in patients with PAH and relate them to the severity of the disease.
  
  
  METHODS
  A microarray screen was performed on total plasma RNA from eight patients with PAH and eight healthy control subjects. Quantitative polymerase chain reaction confirmed reduced miR-150 concentrations and was then used to measure miR-150 levels in (1) two separate cohorts of patients with PAH, from London (n = 145) and Sheffield (n = 30), respectively; (2) circulating microvesicles and blood cells; and (3) lungs from a monocrotaline rat model.
  
  
  RESULTS
  Fifty-eight miRNAs showed differences in plasma concentration and miR-150 the largest down-regulation in PAH. Receiver-operator-characteristic analysis showed both raw and normalized plasma miR-150 levels correlated with 2-year survival (P < 0.01) in patients with PAH. Cox regression analysis confirmed miR-150 levels as a significant predictor of survival. Age, baseline cardiac index, World Health Organization functional class, 6-minute walk distance, disease duration, and red cell distribution width also predicted survival. Entering these covariates in a multivariable model verified plasma miR-150 levels as an independent predictor of survival in PAH (hazard ratio, 0.533; P = 0.010). miR-150 levels also predicted survival in a second, independent PAH cohort. miR-150 levels were significantly reduced in circulating microvesicles from patients with PAH and the lungs of the monocrotaline rat.
  
  
  CONCLUSIONS
  Reduced circulating miR-150 levels are associated with poor survival in PAH.
authors.affiliation: Centre for Pharmacology and Therapeutics, Imperial College London, London, UK.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Rhodes
authors.forename: John
authors.initials: J
authors.lastname: Wharton
authors.forename: Reinier A
authors.initials: RA
authors.lastname: Boon
authors.forename: Tino
authors.initials: T
authors.lastname: Roexe
authors.forename: Hilda
authors.initials: H
authors.lastname: Tsang
authors.forename: Beata
authors.initials: B
authors.lastname: Wojciak-Stothard
authors.forename: Anob
authors.initials: A
authors.lastname: Chakrabarti
authors.forename: Luke S
authors.initials: LS
authors.lastname: Howard
authors.forename: J Simon R
authors.initials: JS
authors.lastname: Gibbs
authors.forename: Allan
authors.initials: A
authors.lastname: Lawrie
authors.forename: Robin
authors.initials: R
authors.lastname: Condliffe
authors.forename: Charles A
authors.initials: CA
authors.lastname: Elliot
authors.forename: David G
authors.initials: DG
authors.lastname: Kiely
authors.forename: Les
authors.initials: L
authors.lastname: Huson
authors.forename: Hossein A
authors.initials: HA
authors.lastname: Ghofrani
authors.forename: Henning
authors.initials: H
authors.lastname: Tiede
authors.forename: Ralph
authors.initials: R
authors.lastname: Schermuly
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Zeiher
authors.forename: Stefanie
authors.initials: S
authors.lastname: Dimmeler
authors.forename: Martin R
authors.initials: MR
authors.lastname: Wilkins
mesh_terms: D000328:Adult; D017677:Age Distribution; D000818:Animals; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D004195:Disease Models, Animal; D015536:Down-Regulation; D065627:Familial Primary Pulmonary Hypertension; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood* / Q000235:genetics*; D008131:London; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D046228:Microarray Analysis / Q000379:methods; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D012372:ROC Curve; D051381:Rats; D012720:Severity of Illness Index; D016019:Survival Analysis
chemical_list: D015415:Biomarkers; D035683:MicroRNAs