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Derivation and characterisation of endothelial cells from patients with chronic thromboembolic pulmonary hypertension.
Tura-Ceide, Olga; Smolders, Valérie F E D; Aventin, Núria; Morén, Constanza; Guitart-Mampel, Mariona; Blanco, Isabel; Piccari, Lucilla; Osorio, Jeisson; Rodríguez, Cristina; Rigol, Montserrat; Solanes, Núria; Malandrino, Andrea; Kurakula, Kondababu; Goumans, Marie Jose; Quax, Paul H A; Peinado, Victor I; Castellà, Manuel; Barberà, Joan Albert.
Afiliación
  • Tura-Ceide O; Department of Pulmonary Medicine, Servei de Pneumologia, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), University of Barcelona, Villarroel, 170, 08036, Barcelona, Spain. olgaturac@gmail.com.
  • Smolders VFED; Biomedical Research Networking Centre on Respiratory Diseases (CIBERES), 28029, Madrid, Spain. olgaturac@gmail.com.
  • Aventin N; Department of Pulmonary Medicine, Santa Caterina Hospital de Salt and the Girona Biomedical Research Institut (IDIBGI), Dr. Josep Trueta University Hospital de Girona, 17190, Girona, Spain. olgaturac@gmail.com.
  • Morén C; Department of Pulmonary Medicine, Servei de Pneumologia, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), University of Barcelona, Villarroel, 170, 08036, Barcelona, Spain.
  • Guitart-Mampel M; Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, Barcelona, Spain.
  • Blanco I; Department of Vascular Surgery, Leiden University Medical Center, Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands.
  • Piccari L; Department of Pulmonary Medicine, Servei de Pneumologia, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), University of Barcelona, Villarroel, 170, 08036, Barcelona, Spain.
  • Osorio J; Laboratory of Muscle Research and Mitochondrial Function, Department of Internal Medicine, Hospital Clínic of Barcelona (HCB), Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), University of Barcelona (UB), Barcelona, Spain.
  • Rodríguez C; Biomedical Research Networking Centre on Rare Diseases (CIBERER), Madrid, Spain.
  • Rigol M; Laboratory of Muscle Research and Mitochondrial Function, Department of Internal Medicine, Hospital Clínic of Barcelona (HCB), Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), University of Barcelona (UB), Barcelona, Spain.
  • Solanes N; Department of Pulmonary Medicine, Servei de Pneumologia, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), University of Barcelona, Villarroel, 170, 08036, Barcelona, Spain.
  • Malandrino A; Biomedical Research Networking Centre on Respiratory Diseases (CIBERES), 28029, Madrid, Spain.
  • Kurakula K; Department of Pulmonary Medicine, Servei de Pneumologia, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), University of Barcelona, Villarroel, 170, 08036, Barcelona, Spain.
  • Goumans MJ; Department of Pulmonary Medicine, Servei de Pneumologia, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), University of Barcelona, Villarroel, 170, 08036, Barcelona, Spain.
  • Quax PHA; Biomedical Research Networking Centre on Respiratory Diseases (CIBERES), 28029, Madrid, Spain.
  • Peinado VI; Department of Pulmonary Medicine, Servei de Pneumologia, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), University of Barcelona, Villarroel, 170, 08036, Barcelona, Spain.
  • Castellà M; Department of Pulmonary Medicine, Santa Caterina Hospital de Salt and the Girona Biomedical Research Institut (IDIBGI), Dr. Josep Trueta University Hospital de Girona, 17190, Girona, Spain.
  • Barberà JA; Cardiovascular Institute, Hospital Clínic de Barcelona-Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
Sci Rep ; 11(1): 18797, 2021 09 22.
Article en En | MEDLINE | ID: mdl-34552142
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.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Embolia Pulmonar / Endotelio Vascular / Hipertensión Pulmonar Tipo de estudio: Observational_studies Límite: Female / Humans / Male / Middle aged Idioma: En Revista: Sci Rep Año: 2021 Tipo del documento: Article País de afiliación: España Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Embolia Pulmonar / Endotelio Vascular / Hipertensión Pulmonar Tipo de estudio: Observational_studies Límite: Female / Humans / Male / Middle aged Idioma: En Revista: Sci Rep Año: 2021 Tipo del documento: Article País de afiliación: España Pais de publicación: Reino Unido