Reduced microRNA-150 is associated with poor survival in pulmonary arterial hypertension

Am J Respir Crit Care Med. 2013 Feb 1;187(3):294-302. doi: 10.1164/rccm.201205-0839OC. Epub 2012 Dec 6.


Rationale: MicroRNAs (miRNAs or miRs) are implicated in the pathogenesis of various cardiovascular diseases, including pulmonary arterial hypertension (PAH).

Objectives: 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.

Measurements and main 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Distribution
  • Animals
  • Biomarkers / blood
  • Cohort Studies
  • Disease Models, Animal
  • Down-Regulation
  • Familial Primary Pulmonary Hypertension
  • Female
  • Humans
  • Hypertension, Pulmonary / blood*
  • Hypertension, Pulmonary / genetics*
  • London
  • Male
  • MicroRNAs / blood*
  • Microarray Analysis / methods
  • Middle Aged
  • Polymerase Chain Reaction / methods
  • ROC Curve
  • Rats
  • Severity of Illness Index
  • Survival Analysis


  • Biomarkers
  • MicroRNAs