@article{6f33f1284d88462ea78cead9c9dab87a,
title = "Metabolic profile in endothelial cells of chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension",
abstract = "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.",
author = "Smolders, {V. F. E. D.} and C. Rodr{\'i}guez and I. Blanco and R. Szulcek and Wim Timens and L. Piccari and Y. Roger and X. Hu and Constanza Mor{\'e}n and C. Bonjoch and L. Sebasti{\'a}n and M. Castell{\`a} and J. Osorio and Peinado, {V. I.} and Bogaard, {Harm Jan} and Quax, {P. H. A.} and M. Cascante and Barber{\`a}, {J. A.} and O. Tura-Ceide",
note = "Funding Information: This research was supported by the funding from a Miguel Servet grant from the Instituto de Salud Carlos III (CP17/00114), the European Commission Horizon 2020 research and innovation program under the MOGLYNET H2020-MSCA-ITN-EJD grant (agreement No 675527), Spanish Society of Respiratory Medicine (SEPAR), Catalan Society of Pneumology (SOCAP), Fundaci{\'o}n Contra la Hipertensi{\'o}n Pulmonar (FCHP) and research grant PI18/00960 from the Institute of Health Carlos III, Spain. Cofunding was provided by the Fondo Europeo de Desarrollo Regional (FEDER); “Una manera de hacer Europa”. HJB and RS were supported by the Dutch Cardiovas-cular Research Alliance: the Dutch Heart Foundation, Dutch Federation of University Medical Centers, the Netherlands Organization for Health Research and Development, and the Royal Netherlands Academy of Sciences Grant 2012–2008 and 2018–2023 awarded to the Phaedra consortium ( http://www.phaedraresearch.nl ). Funding Information: This work was developed at the center de Recerca Biom?dica Cellex, Barcelona, Spain. The authors would like to thank scientific and technologic center of University of Barcelona. Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = feb,
day = "10",
doi = "https://doi.org/10.1038/s41598-022-06238-z",
language = "English",
volume = "12",
journal = "Scientific reports",
issn = "2045-2322",
publisher = "Springer Nature",
number = "1",
}