American journal of respiratory and critical care medicine · 2012
Reduced microRNA-150 is associated with poor survival in pulmonary arterial hypertension.
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Rhodes Christopher J, Wharton John, Boon Reinier A, Roexe Tino, Tsang Hilda, Wojciak-Stothard Beata, Chakrabarti Anob, Howard Luke S, Gibbs J Simon R, Lawrie Allan, Condliffe Robin, Elliot Charles A, Kiely David G, Huson Les, Ghofrani Hossein A, Tiede Henning, Schermuly Ralph, Zeiher Andreas M, Dimmeler Stefanie, Wilkins Martin R
Аннотация
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.
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.