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.

Protein network analyses of pulmonary endothelial cells in chronic thromboembolic pulmonary hypertension / S.B. Nukala, O. Tura-Ceide, G. Aldini, V.F.E.D. Smolders, I. Blanco, V.I. Peinado, M. Castellà, J.A. Barberà, A. Altomare, G. Baron, M. Carini, M. Cascante, A. D’Amato. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 11:1(2021 Mar 10), pp. 5583.1-5583.13. [10.1038/s41598-021-85004-z]

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

S.B. Nukala
Primo
;
G. Aldini;A. Altomare;G. Baron;M. Carini;A. D’Amato
Ultimo
2021

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.
Settore CHIM/01 - Chimica Analitica
Settore BIO/10 - Biochimica
Modulation of glycolytic flux as a new approach for treatment of atherosclerosis and plaque stabilization: a multidisciplinary study (MOGLYNET)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/822088
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