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

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, Martin R. Wilkins*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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 downregulation in PAH. Receiver-operator-characteristic analysis showed both raw and normalized plasma miR-150 levels correlated with 2-year survival (P,0.01) in patientswith 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 alsopredictedsurvival ina 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.

Original languageEnglish
Pages (from-to)294-302
Number of pages9
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume187
Issue number3
DOIs
Publication statusPublished - 1 Feb 2013

Cite this