Metabolic profile in endothelial cells of chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH) are two forms of pulmonary hypertension (PH) characterized by obstructive vasculopathy. Endothelial dysfunction along with metabolic changes towards increased glycolysis are important in PAH pathophysiolo...

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Autores: Smolders, Valérie, Rodríguez, C., Blanco Vich, Isabel, Szulcek, R., Timens, Wim, Piccari, Lucilla, Roger, Y., Hu, X., Morén Núñez, Constanza, Bonjoch, C., Sebastián, L., Castellà Pericàs, Manuel, Osorio, Jeisson, Peinado, Víctor I., Bogaard, Harm Jan, Quax, Paul H. A., Cascante i Serratosa, Marta, Barberà i Mir, Joan Albert, Tura-Ceide, Olga
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2022
País:España
Recursos:Universidad de Barcelona
Repositório:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/186240
Acesso em linha:https://hdl.handle.net/2445/186240
Access Level:Acceso aberto
Palavra-chave:Tromboembolisme
Hipertensió pulmonar
Endoteli
Thromboembolism
Pulmonary hypertension
Endothelium
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spelling Metabolic profile in endothelial cells of chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension.Smolders, ValérieRodríguez, C.Blanco Vich, IsabelSzulcek, R.Timens, WimPiccari, LucillaRoger, Y.Hu, X.Morén Núñez, ConstanzaBonjoch, C.Sebastián, L.Castellà Pericàs, ManuelOsorio, JeissonPeinado, Víctor I.Bogaard, Harm JanQuax, Paul H. A.Cascante i Serratosa, MartaBarberà i Mir, Joan AlbertTura-Ceide, OlgaTromboembolismeHipertensió pulmonarEndoteliThromboembolismPulmonary hypertensionEndotheliumChronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH) are two forms of pulmonary hypertension (PH) characterized by obstructive vasculopathy. Endothelial dysfunction along with metabolic changes towards increased glycolysis are important in PAH pathophysiology. Less is known about such abnormalities in endothelial cells (ECs) from CTEPH patients. This study provides a systematic metabolic comparison of ECs derived from CTEPH and PAH patients. Metabolic gene expression was studied using qPCR in cultured CTEPH-EC and PAH-EC. Western blot analyses were done for HK2, LDHA, PDHA1, PDK and G6PD. Basal viability of CTEPH-EC and PAH-EC with the incubation with metabolic inhibitors was measured using colorimetric viability assays. Human pulmonary artery endothelial cells (HPAEC) were used as healthy controls. Whereas PAH-EC showed significant higher mRNA levels of GLUT1, HK2, LDHA, PDHA1 and GLUD1 metabolic enzymes compared to HPAEC, CTEPH-EC did not. Oxidative phosphorylation associated proteins had an increased expression in PAH-EC compared to CTEPH-EC and HPAEC. PAH-EC, CTEPH-EC and HPAEC presented similar HOXD macrovascular gene expression. Metabolic inhibitors showed a dose-dependent reduction in viability in all three groups, predominantly in PAH-EC. A different metabolic profile is present in CTEPH-EC compared to PAH-EC and suggests differences in molecular mechanisms important in the disease pathology and treatment.Nature Publishing Group2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/186240Articles publicats en revistes (Bioquímica i Biomedicina Molecular)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1038/s41598-022-06238-zScientific Reports, 2022, vol. 12, p. 2283https://doi.org/10.1038/s41598-022-06238-zinfo:eu-repo/grantAgreement/EC/H2020/675527cc-by (c) Smolders, V.F.E.D. et al., 2022https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1862402026-05-27T06:46:51Z
dc.title.none.fl_str_mv Metabolic profile in endothelial cells of chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension.
title Metabolic profile in endothelial cells of chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension.
spellingShingle Metabolic profile in endothelial cells of chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension.
Smolders, Valérie
Tromboembolisme
Hipertensió pulmonar
Endoteli
Thromboembolism
Pulmonary hypertension
Endothelium
title_short Metabolic profile in endothelial cells of chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension.
title_full Metabolic profile in endothelial cells of chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension.
title_fullStr Metabolic profile in endothelial cells of chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension.
title_full_unstemmed Metabolic profile in endothelial cells of chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension.
title_sort Metabolic profile in endothelial cells of chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension.
dc.creator.none.fl_str_mv Smolders, Valérie
Rodríguez, C.
Blanco Vich, Isabel
Szulcek, R.
Timens, Wim
Piccari, Lucilla
Roger, Y.
Hu, X.
Morén Núñez, Constanza
Bonjoch, C.
Sebastián, L.
Castellà Pericàs, Manuel
Osorio, Jeisson
Peinado, Víctor I.
Bogaard, Harm Jan
Quax, Paul H. A.
Cascante i Serratosa, Marta
Barberà i Mir, Joan Albert
Tura-Ceide, Olga
author Smolders, Valérie
author_facet Smolders, Valérie
Rodríguez, C.
Blanco Vich, Isabel
Szulcek, R.
Timens, Wim
Piccari, Lucilla
Roger, Y.
Hu, X.
Morén Núñez, Constanza
Bonjoch, C.
Sebastián, L.
Castellà Pericàs, Manuel
Osorio, Jeisson
Peinado, Víctor I.
Bogaard, Harm Jan
Quax, Paul H. A.
Cascante i Serratosa, Marta
Barberà i Mir, Joan Albert
Tura-Ceide, Olga
author_role author
author2 Rodríguez, C.
Blanco Vich, Isabel
Szulcek, R.
Timens, Wim
Piccari, Lucilla
Roger, Y.
Hu, X.
Morén Núñez, Constanza
Bonjoch, C.
Sebastián, L.
Castellà Pericàs, Manuel
Osorio, Jeisson
Peinado, Víctor I.
Bogaard, Harm Jan
Quax, Paul H. A.
Cascante i Serratosa, Marta
Barberà i Mir, Joan Albert
Tura-Ceide, Olga
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Tromboembolisme
Hipertensió pulmonar
Endoteli
Thromboembolism
Pulmonary hypertension
Endothelium
topic Tromboembolisme
Hipertensió pulmonar
Endoteli
Thromboembolism
Pulmonary hypertension
Endothelium
description Chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH) are two forms of pulmonary hypertension (PH) characterized by obstructive vasculopathy. Endothelial dysfunction along with metabolic changes towards increased glycolysis are important in PAH pathophysiology. Less is known about such abnormalities in endothelial cells (ECs) from CTEPH patients. This study provides a systematic metabolic comparison of ECs derived from CTEPH and PAH patients. Metabolic gene expression was studied using qPCR in cultured CTEPH-EC and PAH-EC. Western blot analyses were done for HK2, LDHA, PDHA1, PDK and G6PD. Basal viability of CTEPH-EC and PAH-EC with the incubation with metabolic inhibitors was measured using colorimetric viability assays. Human pulmonary artery endothelial cells (HPAEC) were used as healthy controls. Whereas PAH-EC showed significant higher mRNA levels of GLUT1, HK2, LDHA, PDHA1 and GLUD1 metabolic enzymes compared to HPAEC, CTEPH-EC did not. Oxidative phosphorylation associated proteins had an increased expression in PAH-EC compared to CTEPH-EC and HPAEC. PAH-EC, CTEPH-EC and HPAEC presented similar HOXD macrovascular gene expression. Metabolic inhibitors showed a dose-dependent reduction in viability in all three groups, predominantly in PAH-EC. A different metabolic profile is present in CTEPH-EC compared to PAH-EC and suggests differences in molecular mechanisms important in the disease pathology and treatment.
publishDate 2022
dc.date.none.fl_str_mv 2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/186240
url https://hdl.handle.net/2445/186240
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1038/s41598-022-06238-z
Scientific Reports, 2022, vol. 12, p. 2283
https://doi.org/10.1038/s41598-022-06238-z
info:eu-repo/grantAgreement/EC/H2020/675527
dc.rights.none.fl_str_mv cc-by (c) Smolders, V.F.E.D. et al., 2022
https://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Smolders, V.F.E.D. et al., 2022
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv Articles publicats en revistes (Bioquímica i Biomedicina Molecular)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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