Journalartikel
Autorenliste: 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; Condliffes, Robin; Elliot, Charles A.; Kielys, David G.; Huson, Les; Ghofrani, Hossein A.; Tiede, Henning; Schermuly, Ralph; Zeihers, Andreas M.; Dimmeler, Stefanie; Wilkins, Martin R.
Jahr der Veröffentlichung: 2013
Seiten: 294-302
Zeitschrift: American Journal of Respiratory and Critical Care Medicine
Bandnummer: 187
Heftnummer: 3
ISSN: 1073-449X
eISSN: 1535-4970
DOI Link: https://doi.org/10.1164/rccm.201205-0839OC
Verlag: American Thoracic Society
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 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.
Abstract:
Zitierstile
Harvard-Zitierstil: Rhodes, C., Wharton, J., Boon, R., Roexe, T., Tsang, H., Wojciak-Stothard, B., et al. (2013) Reduced MicroRNA-150 Is Associated with Poor Survival in Pulmonary Arterial Hypertension, American Journal of Respiratory and Critical Care Medicine, 187(3), pp. 294-302. https://doi.org/10.1164/rccm.201205-0839OC
APA-Zitierstil: Rhodes, C., Wharton, J., Boon, R., Roexe, T., Tsang, H., Wojciak-Stothard, B., Chakrabarti, A., Howard, L., Gibbs, J., Lawrie, A., Condliffes, R., Elliot, C., Kielys, D., Huson, L., Ghofrani, H., Tiede, H., Schermuly, R., Zeihers, A., Dimmeler, S., ...Wilkins, M. (2013). Reduced MicroRNA-150 Is Associated with Poor Survival in Pulmonary Arterial Hypertension. American Journal of Respiratory and Critical Care Medicine. 187(3), 294-302. https://doi.org/10.1164/rccm.201205-0839OC
Schlagwörter
CIRCULATING MICRORNAS; miR-150; NOTCH3; prognostic biomarkers; Pulmonary hypertension
