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Reduced microRNA-150 is associated with poor survival in pulmonary arterial hypertension
Christopher J Rhodes1, John Wharton, Reinier A Boon
1Centre for Pharmacology and Therapeutics, Imperial College London, London, UK.
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.
Insights
Reduced levels of microRNA-150 (miR-150) in pulmonary arterial hypertension (PAH) patients are linked to poorer survival. This finding could aid in predicting PAH patient outcomes.
Area of Science:
- Cardiovascular Research
- Molecular Biology
- Biomarker Discovery
Background:
- MicroRNAs (miRNAs) play a role in cardiovascular diseases, including pulmonary arterial hypertension (PAH).
- Understanding miRNA involvement in PAH pathogenesis is crucial for developing diagnostic and prognostic tools.
Purpose of the Study:
- To quantify plasma miRNA levels in PAH patients.
- To correlate these levels with disease severity and patient survival.
Main Methods:
- Microarray screening of plasma RNA from PAH patients and healthy controls.
- Quantitative PCR validation of miR-150 levels in independent PAH cohorts, microvesicles, blood cells, and a rat PAH model.
Main Results:
- Plasma miR-150 was significantly down-regulated in PAH patients.
- Lower miR-150 levels strongly correlated with reduced 2-year survival in PAH.
- miR-150 independently predicted survival in multivariable analysis.
Conclusions:
- Decreased circulating miR-150 levels serve as a significant prognostic biomarker for poor survival in pulmonary arterial hypertension.
- Reduced miR-150 was observed in microvesicles and lungs of PAH models.
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