TY - JOUR
T1 - Reduced microrna-150 is associated with poor survival in pulmonary arterial hypertension
AU - Rhodes, Christopher J.
AU - Wharton, John
AU - Boon, Reinier A.
AU - Roexe, Tino
AU - Tsang, Hilda
AU - Wojciak-Stothard, Beata
AU - Chakrabarti, Anob
AU - Howard, Luke S.
AU - Gibbs, J. Simon R.
AU - Lawrie, Allan
AU - Condliffe, Robin
AU - Elliot, Charles A.
AU - Kiely, David G.
AU - Huson, Les
AU - Ghofrani, Hossein A.
AU - Tiede, Henning
AU - Schermuly, Ralph
AU - Zeiher, Andreas M.
AU - Dimmeler, Stefanie
AU - Wilkins, Martin R.
PY - 2013/2/1
Y1 - 2013/2/1
N2 - 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.
AB - 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.
KW - MicroRNA
KW - MiR-150
KW - Prognostic biomarkers
KW - Pulmonary hypertension
UR - http://www.scopus.com/inward/record.url?scp=84873399404&partnerID=8YFLogxK
U2 - 10.1164/rccm.201205-0839OC
DO - 10.1164/rccm.201205-0839OC
M3 - Article
C2 - 23220912
AN - SCOPUS:84873399404
VL - 187
SP - 294
EP - 302
JO - American Journal of Respiratory and Critical Care Medicine
JF - American Journal of Respiratory and Critical Care Medicine
SN - 1073-449X
IS - 3
ER -