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An explorative metabolomic analysis of the endothelium in pulmonary hypertension

Pulmonary hypertension (PH) is classified into five clinical diagnostic groups, including group 1 [idiopathic pulmonary arterial hypertension (IPAH) and connective tissue disease-associated PAH (CTD-aPAH)] and group 4 (chronic thromboembolic pulmonary hypertension (CTEPH)). PH is a progressive, life...

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Autores principales: Carlsen, J., Henriksen, H. H., Marin de Mas, I., Johansson, P. I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9345936/
https://www.ncbi.nlm.nih.gov/pubmed/35918401
http://dx.doi.org/10.1038/s41598-022-17374-x
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author Carlsen, J.
Henriksen, H. H.
Marin de Mas, I.
Johansson, P. I.
author_facet Carlsen, J.
Henriksen, H. H.
Marin de Mas, I.
Johansson, P. I.
author_sort Carlsen, J.
collection PubMed
description Pulmonary hypertension (PH) is classified into five clinical diagnostic groups, including group 1 [idiopathic pulmonary arterial hypertension (IPAH) and connective tissue disease-associated PAH (CTD-aPAH)] and group 4 (chronic thromboembolic pulmonary hypertension (CTEPH)). PH is a progressive, life-threatening, incurable disease. The pathological mechanisms underlying PH remain elusive; recent evidence has revealed that abnormal metabolic activities in the endothelium may play a crucial role. This research introduces a novel approach for studying PH endothelial function, building on the genome-scale metabolic reconstruction of the endothelial cell (EC) to investigate intracellular metabolism. We demonstrate that the intracellular metabolic activities of ECs in PH patients cluster into four phenotypes independent of the PH diagnosis. Notably, the disease severity differs significantly between the metabolic phenotypes, suggesting their clinical relevance. The significant metabolic differences between the PH phenotypes indicate that they may require different therapeutic interventions. In addition, diagnostic capabilities enabling their identification is warranted to investigate whether this opens a novel avenue of precision medicine.
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spelling pubmed-93459362022-08-04 An explorative metabolomic analysis of the endothelium in pulmonary hypertension Carlsen, J. Henriksen, H. H. Marin de Mas, I. Johansson, P. I. Sci Rep Article Pulmonary hypertension (PH) is classified into five clinical diagnostic groups, including group 1 [idiopathic pulmonary arterial hypertension (IPAH) and connective tissue disease-associated PAH (CTD-aPAH)] and group 4 (chronic thromboembolic pulmonary hypertension (CTEPH)). PH is a progressive, life-threatening, incurable disease. The pathological mechanisms underlying PH remain elusive; recent evidence has revealed that abnormal metabolic activities in the endothelium may play a crucial role. This research introduces a novel approach for studying PH endothelial function, building on the genome-scale metabolic reconstruction of the endothelial cell (EC) to investigate intracellular metabolism. We demonstrate that the intracellular metabolic activities of ECs in PH patients cluster into four phenotypes independent of the PH diagnosis. Notably, the disease severity differs significantly between the metabolic phenotypes, suggesting their clinical relevance. The significant metabolic differences between the PH phenotypes indicate that they may require different therapeutic interventions. In addition, diagnostic capabilities enabling their identification is warranted to investigate whether this opens a novel avenue of precision medicine. Nature Publishing Group UK 2022-08-02 /pmc/articles/PMC9345936/ /pubmed/35918401 http://dx.doi.org/10.1038/s41598-022-17374-x Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Carlsen, J.
Henriksen, H. H.
Marin de Mas, I.
Johansson, P. I.
An explorative metabolomic analysis of the endothelium in pulmonary hypertension
title An explorative metabolomic analysis of the endothelium in pulmonary hypertension
title_full An explorative metabolomic analysis of the endothelium in pulmonary hypertension
title_fullStr An explorative metabolomic analysis of the endothelium in pulmonary hypertension
title_full_unstemmed An explorative metabolomic analysis of the endothelium in pulmonary hypertension
title_short An explorative metabolomic analysis of the endothelium in pulmonary hypertension
title_sort explorative metabolomic analysis of the endothelium in pulmonary hypertension
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9345936/
https://www.ncbi.nlm.nih.gov/pubmed/35918401
http://dx.doi.org/10.1038/s41598-022-17374-x
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