Imperial College London

Professor Martin Wilkins

Faculty of MedicineDepartment of Medicine

Head of the Department of Medicine
 
 
 
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Contact

 

+44 (0)20 3313 2049m.wilkins

 
 
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Location

 

NIHR / Wellcome Trust Clinical Research FacilityICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Rhodes:2016:10.1161/CIRCULATIONAHA.116.024602,
author = {Rhodes, CJ and Ghataorhe, P and Wharton, J and Rue-Albrecht, KC and Hadinnapola, C and Watson, G and Bleda, M and Haimel, M and Coghlan, G and Corris, PA and Howard, LS and Kiely, DG and Peacock, AJ and Pepke-Zaba, J and Toshner, MR and Wort, SJ and Gibbs, SR and Lawrie, A and Graf, S and Morrell, NW and Wilkins, MR},
doi = {10.1161/CIRCULATIONAHA.116.024602},
journal = {Circulation},
pages = {460--475},
title = {Plasma metabolomics implicate modified transfer RNAs and altered bioenergetics in the outcome of pulmonary arterial hypertension},
url = {http://dx.doi.org/10.1161/CIRCULATIONAHA.116.024602},
volume = {135},
year = {2016}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Background: Pulmonary arterial hypertension (PAH) is a heterogeneous disorder with high mortality.Methods: We conducted a comprehensive study of plasma metabolites using ultraperformance liquid chromatography mass spectrometry to identify patients at high risk of early death, to identify patients who respond well to treatment, and to provide novel molecular insights into disease pathogenesis.Results: Fifty-three circulating metabolites distinguished well-phenotyped patients with idiopathic or heritable PAH (n=365) from healthy control subjects (n=121) after correction for multiple testing (P<7.3e-5) and confounding factors, including drug therapy, and renal and hepatic impairment. A subset of 20 of 53 metabolites also discriminated patients with PAH from disease control subjects (symptomatic patients without pulmonary hypertension, n=139). Sixty-two metabolites were prognostic in PAH, with 36 of 62 independent of established prognostic markers. Increased levels of tRNA-specific modified nucleosides (N2,N2-dimethylguanosine, N1-methylinosine), tricarboxylic acid cycle intermediates (malate, fumarate), glutamate, fatty acid acylcarnitines, tryptophan, and polyamine metabolites and decreased levels of steroids, sphingomyelins, and phosphatidylcholines distinguished patients from control subjects. The largest differences correlated with increased risk of death, and correction of several metabolites over time was associated with a better outcome. Patients who responded to calcium channel blocker therapy had metabolic profiles similar to those of healthy control subjects.Conclusions: Metabolic profiles in PAH are strongly related to survival and should be considered part of the deep phenotypic characterization of this disease. Our results support the investigation of targeted therapeutic strategies that seek to address the alterations in translational regulation and energy metabolism that characterize these patients.
AU - Rhodes,CJ
AU - Ghataorhe,P
AU - Wharton,J
AU - Rue-Albrecht,KC
AU - Hadinnapola,C
AU - Watson,G
AU - Bleda,M
AU - Haimel,M
AU - Coghlan,G
AU - Corris,PA
AU - Howard,LS
AU - Kiely,DG
AU - Peacock,AJ
AU - Pepke-Zaba,J
AU - Toshner,MR
AU - Wort,SJ
AU - Gibbs,SR
AU - Lawrie,A
AU - Graf,S
AU - Morrell,NW
AU - Wilkins,MR
DO - 10.1161/CIRCULATIONAHA.116.024602
EP - 475
PY - 2016///
SN - 0009-7322
SP - 460
TI - Plasma metabolomics implicate modified transfer RNAs and altered bioenergetics in the outcome of pulmonary arterial hypertension
T2 - Circulation
UR - http://dx.doi.org/10.1161/CIRCULATIONAHA.116.024602
UR - http://hdl.handle.net/10044/1/43969
VL - 135
ER -