Protein network analyses of pulmonary endothelial cells in chronic thromboembolic pulmonary hypertension

Abstract Chronic thromboembolic pulmonary hypertension (CTEPH) is a vascular disease characterized by the presence of organized thromboembolic material in pulmonary arteries leading to increased vascular resistance, heart failure and death. Dysfunction of endothelial cells is involved in CTEPH. The...

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Autores principales: Sarath Babu Nukala, Olga Tura-Ceide, Giancarlo Aldini, Valérie F. E. D. Smolders, Isabel Blanco, Victor I. Peinado, Manuel Castellà, Joan Albert Barberà, Alessandra Altomare, Giovanna Baron, Marina Carini, Marta Cascante, Alfonsina D’Amato
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:5b58cd2d35b441059203f2fa2fb851ca2021-12-02T13:34:33ZProtein network analyses of pulmonary endothelial cells in chronic thromboembolic pulmonary hypertension10.1038/s41598-021-85004-z2045-2322https://doaj.org/article/5b58cd2d35b441059203f2fa2fb851ca2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85004-zhttps://doaj.org/toc/2045-2322Abstract Chronic thromboembolic pulmonary hypertension (CTEPH) is a vascular disease characterized by the presence of organized thromboembolic material in pulmonary arteries leading to increased vascular resistance, heart failure and death. Dysfunction of endothelial cells is involved in CTEPH. The present study describes for the first time the molecular processes underlying endothelial dysfunction in the development of the CTEPH. The advanced analytical approach and the protein network analyses of patient derived CTEPH endothelial cells allowed the quantitation of 3258 proteins. The 673 differentially regulated proteins were associated with functional and disease protein network modules. The protein network analyses resulted in the characterization of dysregulated pathways associated with endothelial dysfunction, such as mitochondrial dysfunction, oxidative phosphorylation, sirtuin signaling, inflammatory response, oxidative stress and fatty acid metabolism related pathways. In addition, the quantification of advanced oxidation protein products, total protein carbonyl content, and intracellular reactive oxygen species resulted increased attesting the dysregulation of oxidative stress response. In conclusion this is the first quantitative study to highlight the involvement of endothelial dysfunction in CTEPH using patient samples and by network medicine approach.Sarath Babu NukalaOlga Tura-CeideGiancarlo AldiniValérie F. E. D. SmoldersIsabel BlancoVictor I. PeinadoManuel CastellàJoan Albert BarberàAlessandra AltomareGiovanna BaronMarina CariniMarta CascanteAlfonsina D’AmatoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Sarath Babu Nukala
Olga Tura-Ceide
Giancarlo Aldini
Valérie F. E. D. Smolders
Isabel Blanco
Victor I. Peinado
Manuel Castellà
Joan Albert Barberà
Alessandra Altomare
Giovanna Baron
Marina Carini
Marta Cascante
Alfonsina D’Amato
Protein network analyses of pulmonary endothelial cells in chronic thromboembolic pulmonary hypertension
description Abstract Chronic thromboembolic pulmonary hypertension (CTEPH) is a vascular disease characterized by the presence of organized thromboembolic material in pulmonary arteries leading to increased vascular resistance, heart failure and death. Dysfunction of endothelial cells is involved in CTEPH. The present study describes for the first time the molecular processes underlying endothelial dysfunction in the development of the CTEPH. The advanced analytical approach and the protein network analyses of patient derived CTEPH endothelial cells allowed the quantitation of 3258 proteins. The 673 differentially regulated proteins were associated with functional and disease protein network modules. The protein network analyses resulted in the characterization of dysregulated pathways associated with endothelial dysfunction, such as mitochondrial dysfunction, oxidative phosphorylation, sirtuin signaling, inflammatory response, oxidative stress and fatty acid metabolism related pathways. In addition, the quantification of advanced oxidation protein products, total protein carbonyl content, and intracellular reactive oxygen species resulted increased attesting the dysregulation of oxidative stress response. In conclusion this is the first quantitative study to highlight the involvement of endothelial dysfunction in CTEPH using patient samples and by network medicine approach.
format article
author Sarath Babu Nukala
Olga Tura-Ceide
Giancarlo Aldini
Valérie F. E. D. Smolders
Isabel Blanco
Victor I. Peinado
Manuel Castellà
Joan Albert Barberà
Alessandra Altomare
Giovanna Baron
Marina Carini
Marta Cascante
Alfonsina D’Amato
author_facet Sarath Babu Nukala
Olga Tura-Ceide
Giancarlo Aldini
Valérie F. E. D. Smolders
Isabel Blanco
Victor I. Peinado
Manuel Castellà
Joan Albert Barberà
Alessandra Altomare
Giovanna Baron
Marina Carini
Marta Cascante
Alfonsina D’Amato
author_sort Sarath Babu Nukala
title Protein network analyses of pulmonary endothelial cells in chronic thromboembolic pulmonary hypertension
title_short Protein network analyses of pulmonary endothelial cells in chronic thromboembolic pulmonary hypertension
title_full Protein network analyses of pulmonary endothelial cells in chronic thromboembolic pulmonary hypertension
title_fullStr Protein network analyses of pulmonary endothelial cells in chronic thromboembolic pulmonary hypertension
title_full_unstemmed Protein network analyses of pulmonary endothelial cells in chronic thromboembolic pulmonary hypertension
title_sort protein network analyses of pulmonary endothelial cells in chronic thromboembolic pulmonary hypertension
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/5b58cd2d35b441059203f2fa2fb851ca
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