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

Sci Rep. 2021 Mar 10;11(1):5583.doi: 10.1038/s41598-021-85004-z.

Fecha de la publicación: 10/03/2021

Autor: Sarath Babu Nukala (# 1, 2), Olga Tura-Ceide (# 3, 4, 5), Giancarlo Aldini (6), Valérie F E D Smolders (7, 3), Isabel Blanco (3, 4), Victor I Peinado (3, 4), Manuel Castellà (8), Joan Albert Barberà (3, 4), Alessandra Altomare (6), Giovanna Baron 6, Marina Carini (6), Marta Cascante (# 7, 9), Alfonsina D'Amato(# 10)


PMID: 33692478P

MCID: PMC7946953

DOI: 10.1038/s41598-021-85004-z

Free PMC article


1-.Department of Pharmaceutical Sciences, UniversitàDegliStudiDi Milano, 20133, Milan, Italy.
2-.Department of Pharmacology, The University of Illinois College of Medicine, 909 S Wolcott Ave, COMRB 4097, Chicago, IL, 60612, USA.
3-.Department of Pulmonary Medicine, Hospital Clínic-InstitutD’InvestigacionsBiomèdiques August Pi I Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
4-.Centro de InvestigaciónBiomédicaen Red de EnfermedadesRespiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), CB06/06/0011, Madrid, Spain.
5-.Department of Pulmonary Medicine, Dr. JosepTrueta University Hospital de Girona, Santa Caterina Hospital de Salt and the Girona Biomedical Research Institut (IDIBGI), Girona, Spain.
6-.Department of Pharmaceutical Sciences, UniversitàDegliStudiDi Milano, 20133, Milan, Italy.
7-.Department of Biochemistry and Molecular Biomedicine and Institute of Biomedicine (IBUB), Faculty of Biology, University of Barcelona, Barcelona, Spain.
8-.Department of Cardiovascular Surgery, InstitutClínic del Tòrax, Hospital Clínic, University of Barcelona, Barcelona, Spain.
9-.Centro de InvestigaciónBiomédicaen Red de EnfermedadesHepáticas y Digestivas (CIBEREHD)- CB17/04/00023 and Metabolomics Node At INB-Bioinfarmatics Platform, Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
10-.Department of Pharmaceutical Sciences, UniversitàDegliStudiDi Milano, 20133, Milan, Italy.
#Contributed equally.


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.