Derivation and characterisation of endothelial cells from patients with chronic thromboembolic pulmonary hypertension

Abstract Pulmonary endarterectomy (PEA) resected material offers a unique opportunity to develop an in vitro endothelial cell model of chronic thromboembolic pulmonary hypertension (CTEPH). We aimed to comprehensively analyze the endothelial function, molecular signature, and mitochondrial profile o...

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Autores principales:	Olga Tura-Ceide, Valérie F. E. D. Smolders, Núria Aventin, Constanza Morén, Mariona Guitart-Mampel, Isabel Blanco, Lucilla Piccari, Jeisson Osorio, Cristina Rodríguez, Montserrat Rigol, Núria Solanes, Andrea Malandrino, Kondababu Kurakula, Marie Jose Goumans, Paul H. A. Quax, Victor I. Peinado, Manuel Castellà, Joan Albert Barberà
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/754ae83577394ffaaec8967753372381
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spelling	oai:doaj.org-article:754ae83577394ffaaec89677533723812021-12-02T18:48:01ZDerivation and characterisation of endothelial cells from patients with chronic thromboembolic pulmonary hypertension10.1038/s41598-021-98320-12045-2322https://doaj.org/article/754ae83577394ffaaec89677533723812021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98320-1https://doaj.org/toc/2045-2322Abstract Pulmonary endarterectomy (PEA) resected material offers a unique opportunity to develop an in vitro endothelial cell model of chronic thromboembolic pulmonary hypertension (CTEPH). We aimed to comprehensively analyze the endothelial function, molecular signature, and mitochondrial profile of CTEPH-derived endothelial cells to better understand the pathophysiological mechanisms of endothelial dysfunction behind CTEPH, and to identify potential novel targets for the prevention and treatment of the disease. Isolated cells from specimens obtained at PEA (CTEPH-EC), were characterized based on morphology, phenotype, and functional analyses (in vitro and in vivo tubule formation, proliferation, apoptosis, and migration). Mitochondrial content, morphology, and dynamics, as well as high-resolution respirometry and oxidative stress, were also studied. CTEPH-EC displayed a hyperproliferative phenotype with an increase expression of adhesion molecules and a decreased apoptosis, eNOS activity, migration capacity and reduced angiogenic capacity in vitro and in vivo compared to healthy endothelial cells. CTEPH-EC presented altered mitochondrial dynamics, increased mitochondrial respiration and an unbalanced production of reactive oxygen species and antioxidants. Our study is the foremost comprehensive investigation of CTEPH-EC. Modulation of redox, mitochondrial homeostasis and adhesion molecule overexpression arise as novel targets and biomarkers in CTEPH.Olga Tura-CeideValérie F. E. D. SmoldersNúria AventinConstanza MorénMariona Guitart-MampelIsabel BlancoLucilla PiccariJeisson OsorioCristina RodríguezMontserrat RigolNúria SolanesAndrea MalandrinoKondababu KurakulaMarie Jose GoumansPaul H. A. QuaxVictor I. PeinadoManuel CastellàJoan Albert BarberàNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Olga Tura-Ceide Valérie F. E. D. Smolders Núria Aventin Constanza Morén Mariona Guitart-Mampel Isabel Blanco Lucilla Piccari Jeisson Osorio Cristina Rodríguez Montserrat Rigol Núria Solanes Andrea Malandrino Kondababu Kurakula Marie Jose Goumans Paul H. A. Quax Victor I. Peinado Manuel Castellà Joan Albert Barberà Derivation and characterisation of endothelial cells from patients with chronic thromboembolic pulmonary hypertension
description	Abstract Pulmonary endarterectomy (PEA) resected material offers a unique opportunity to develop an in vitro endothelial cell model of chronic thromboembolic pulmonary hypertension (CTEPH). We aimed to comprehensively analyze the endothelial function, molecular signature, and mitochondrial profile of CTEPH-derived endothelial cells to better understand the pathophysiological mechanisms of endothelial dysfunction behind CTEPH, and to identify potential novel targets for the prevention and treatment of the disease. Isolated cells from specimens obtained at PEA (CTEPH-EC), were characterized based on morphology, phenotype, and functional analyses (in vitro and in vivo tubule formation, proliferation, apoptosis, and migration). Mitochondrial content, morphology, and dynamics, as well as high-resolution respirometry and oxidative stress, were also studied. CTEPH-EC displayed a hyperproliferative phenotype with an increase expression of adhesion molecules and a decreased apoptosis, eNOS activity, migration capacity and reduced angiogenic capacity in vitro and in vivo compared to healthy endothelial cells. CTEPH-EC presented altered mitochondrial dynamics, increased mitochondrial respiration and an unbalanced production of reactive oxygen species and antioxidants. Our study is the foremost comprehensive investigation of CTEPH-EC. Modulation of redox, mitochondrial homeostasis and adhesion molecule overexpression arise as novel targets and biomarkers in CTEPH.
format	article
author	Olga Tura-Ceide Valérie F. E. D. Smolders Núria Aventin Constanza Morén Mariona Guitart-Mampel Isabel Blanco Lucilla Piccari Jeisson Osorio Cristina Rodríguez Montserrat Rigol Núria Solanes Andrea Malandrino Kondababu Kurakula Marie Jose Goumans Paul H. A. Quax Victor I. Peinado Manuel Castellà Joan Albert Barberà
author_facet	Olga Tura-Ceide Valérie F. E. D. Smolders Núria Aventin Constanza Morén Mariona Guitart-Mampel Isabel Blanco Lucilla Piccari Jeisson Osorio Cristina Rodríguez Montserrat Rigol Núria Solanes Andrea Malandrino Kondababu Kurakula Marie Jose Goumans Paul H. A. Quax Victor I. Peinado Manuel Castellà Joan Albert Barberà
author_sort	Olga Tura-Ceide
title	Derivation and characterisation of endothelial cells from patients with chronic thromboembolic pulmonary hypertension
title_short	Derivation and characterisation of endothelial cells from patients with chronic thromboembolic pulmonary hypertension
title_full	Derivation and characterisation of endothelial cells from patients with chronic thromboembolic pulmonary hypertension
title_fullStr	Derivation and characterisation of endothelial cells from patients with chronic thromboembolic pulmonary hypertension
title_full_unstemmed	Derivation and characterisation of endothelial cells from patients with chronic thromboembolic pulmonary hypertension
title_sort	derivation and characterisation of endothelial cells from patients with chronic thromboembolic pulmonary hypertension
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/754ae83577394ffaaec8967753372381
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Derivation and characterisation of endothelial cells from patients with chronic thromboembolic pulmonary hypertension

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