• Christopher J Rhodes, John Wharton, Reinier A Boon, Tino Roexe, Hilda Tsang, Beata Wojciak-Stothard, Anob Chakrabarti, Luke S Howard, J Simon R Gibbs, Allan Lawrie, Robin Condliffe, Charles A Elliot, David G Kiely, Les Huson, Hossein A Ghofrani, Henning Tiede, Ralph Schermuly, Andreas M Zeiher, Stefanie Dimmeler, and Martin R Wilkins.
• Centre for Pharmacology and Therapeutics, Imperial College London, London, UK.
• Am. J. Respir. Crit. Care Med. 2013 Feb 1; 187 (3): 294-302.

RationaleMicroRNAs (miRNAs or miRs) are implicated in the pathogenesis of various cardiovascular diseases, including pulmonary arterial hypertension (PAH).ObjectivesWe sought to measure changes in plasma levels of miRNAs in patients with PAH and relate them to the severity of the disease.MethodsA 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 ResultsFifty-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.ConclusionsReduced circulating miR-150 levels are associated with poor survival in PAH.

31 keywords...

hide…