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Title: Derivation and characterisation of endothelial cells from patients with chronic thromboembolic pulmonary hypertension
Author: Tura-Ceide, Olga
Smolders, Valérie
Aventin, Núria
Morén Núñez, Constanza
Guitart Mampel, Mariona
Blanco Vich, Isabel
Piccari, Lucilla
Osorio, Jeisson
Rodríguez, Cristina
Rigol, Montserrat
Solanes, Núria
Malandrino, Andrea
Kurakula, Kondababu
Goumans, Marie José
Quax, Paul H. A.
Peinado Cabré, Víctor Ivo
Castellà, Manuel
Barberà i Mir, Joan Albert
Keywords: Embòlia pulmonar
Hipertensió pulmonar
Pulmonary embolism
Pulmonary hypertension
Issue Date: 22-Sep-2021
Publisher: Nature Publishing Group
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.
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It is part of: Scientific Reports, 2021, vol. 11, num. 1, p. 18797
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ISSN: 2045-2322
Appears in Collections:Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Publicacions de projectes de recerca finançats per la UE
Articles publicats en revistes (Institut de Bioenginyeria de Catalunya (IBEC))
Articles publicats en revistes (Medicina)

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