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Chouvarine, P.* ; Giera, M.* ; Kastenmüller, G. ; Artati, A. ; Adamski, J. ; Bertram, H.* ; Hansmann, G.*

Trans-right ventricle and transpulmonary metabolite gradients in human pulmonary arterial hypertension.

Heart 106, 1332-1341 (2020)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Objective While metabolic dysfunction occurs in several pulmonary arterial hypertension (PAH) animal models, its role in the human hypertensive right ventricle (RV) and lung is not well characterised. We investigated whether circulating metabolite concentrations differ across the hypertensive RV and/or the pulmonary circulation, and correlate with invasive haemodynamic/echocardiographic variables in patients with PAH.Methods Prospective EDTA blood collection during cardiac catheterisation from the superior vena cava (SVC), pulmonary artery (PA) and ascending aorta (AAO) in children with PAH (no shunt) and non-PAH controls (Con), followed by unbiased screens of 427 metabolites and 836 lipid species and fatty acids (FAs) in blood plasma (Metabolon and Lipidyzer platforms). Metabolite concentrations were correlated with echocardiographic and invasive haemodynamic variables.Results Metabolomics/lipidomics analysis of differential concentrations (false discovery rate<0.15) revealed several metabolite gradients in the trans-RV (PA vs SVC) setting. Notably, dicarboxylic acids (eg, octadecanedioate: fold change (FC)_Control=0.77, FC_PAH=1.09, p value=0.044) and acylcarnitines (eg, stearoylcarnitine: FC_Control=0.74, FC_PAH=1.21, p value=0.058). Differentially regulated metabolites were also found in the transpulmonary (AAO vs PA) setting and between-group comparisons, that is, in the SVC (PAH-S VC vs Con-S VC), PA and AAO. Importantly, the differential PAH-metabolite concentrations correlated with numerous outcome-relevant variables (e.g., tricuspid annular plane systolic excursion, pulmonary vascular resistance).Conclusions In PAH, trans-RV and transpulmonary metabolite gradients exist and correlate with haemodynamic determinants of clinical outcome. The most pronounced differential trans-R V gradients are known to be involved in lipid metabolism/lipotoxicity, that is, accumulation of long chain FAs. The identified accumulation of dicarboxylic acids and acylcarnitines likely indicates impaired beta-oxidation in the hypertensive RV and represents emerging biomarkers and therapeutic targets in PAH.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Biomarker ; Hemodynamics ; Human ; Lipidomics ; Metabolites ; Metabolomics ; Omics ; Pah ; Trans-rv Gradient ; Transpulmonary Gradient ; β-oxidation; Heart-failure; Lipotoxicity; Oxidation; Children; Alpha
ISSN (print) / ISBN 1355-6037
e-ISSN 1468-201X
Zeitschrift Heart
Quellenangaben Band: 106, Heft: 17, Seiten: 1332-1341 Artikelnummer: , Supplement: ,
Verlag BMJ Publishing Group
Verlagsort British Med Assoc House, Tavistock Square, London Wc1h 9jr, England
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Bioinformatics and Systems Biology (IBIS)
CF Metabolomics & Proteomics (CF-MPC)
Molekulare Endokrinologie und Metabolismus (MEM)