96 results on '"Tura-Ceide, O."'
Search Results
2. Different Proteomic Profiles in Severe Pulmonary Hypertension Associated With COPD and Pulmonary Fibrosis
- Author
-
Bosacoma Armora, A., primary, Garcia, A.R., additional, Lozano, J., additional, Sidorova, J., additional, Blanco, I., additional, Martín, C., additional, Tura-Ceide, O., additional, Peinado, V.I., additional, Rodríguez, D., additional, López-Meseguer, M., additional, Hernandez-Gonzalez, F., additional, Ribas, J., additional, Pomares, X., additional, Santos, S., additional, Molina-Molina, M., additional, Sellares Torres, J., additional, and Barbera, J.A., additional
- Published
- 2024
- Full Text
- View/download PDF
3. Metabolic profile in endothelial cells of chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension
- Author
-
Smolders, V. F. E. D., Rodríguez, C., Blanco, I., Szulcek, R., Timens, Wim, Piccari, L., Roger, Y., Hu, X., Morén, Constanza, Bonjoch, C., Sebastián, L., Castellà, M., Osorio, J., Peinado, V. I., Bogaard, Harm Jan, Quax, P. H. A., Cascante, M., Barberà, J. A., and Tura-Ceide, O.
- Published
- 2022
- Full Text
- View/download PDF
4. Targeting the Main Anatomopathological Features in Animal Models of Myocardial Infarction
- Author
-
Solanes, N., Bobi, J., Dagleish, M.P., Jiménez, F.R., Gray, G.A., Sabaté, M., Tura-Ceide, O., and Rigol, M.
- Published
- 2020
- Full Text
- View/download PDF
5. Association Between Systemic and Pulmonary Vascular Dysfunction in COPD
- Author
-
Piccari L, Del Pozo R, Blanco I, García-Lucio J, Torralba Y, Tura-Ceide O, Moises J, Sitges M, Peinado VI, and Barberà JA
- Subjects
copd ,pulmonary circulation and pulmonary hypertension ,emphysema ,cardiovascular diseases ,Diseases of the respiratory system ,RC705-779 - Abstract
Lucilla Piccari,1 Roberto Del Pozo,1 Isabel Blanco,1,2 Jessica García-Lucio,1 Yolanda Torralba,1,2 Olga Tura-Ceide,1,2 Jorge Moises,1,2 Marta Sitges,3,4 Víctor Ivo Peinado,1,2 Joan Albert Barberà1,2 1Department of Pulmonary Medicine, Hospital Clínic, Institute of Biomedical Research August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain; 2Biomedical Research Networking Centre on Respiratory Diseases (CIBERES), Madrid, Spain; 3Department of Cardiology, Hospital Clínic, Institute of Biomedical Research August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Barcelona, Spain; 4Biomedical Research Networking Centre on Cardiovascular Diseases (CIBERCV), Madrid, SpainCorrespondence: Joan Albert BarberàDepartment of Pulmonary Medicine, Hospital Clínic, Institute of Biomedical Research August Pi i Sunyer (IDIBAPS), University of Barcelona, Villarroel 170, Barcelona 08036, SpainTel +34 932275779Email jbarbera@clinic.catIntroduction: In chronic obstructive pulmonary disease (COPD), endothelial dysfunction and stiffness of systemic arteries may contribute to increased cardiovascular risk. Pulmonary vascular disease (PVD) is frequent in COPD. The association between PVD and systemic vascular dysfunction has not been thoroughly evaluated in COPD.Methods: A total of 108 subjects were allocated into four groups (non-smoking controls, smoking controls, COPD without PVD and COPD with PVD). In systemic arteries, endothelial dysfunction was assessed by flow-mediated dilation (FMD) and arterial stiffness by pulse wave analysis (PWA) and pulse wave velocity (PWV). PVD was defined by a mean pulmonary artery pressure (PAP) ≥ 25 mmHg at right heart catheterization or by a tricuspid regurgitation velocity > 2.8 m/s at doppler echocardiography. Biomarkers of inflammation and endothelial damage were assessed in peripheral blood.Results: FMD was lower in COPD patients, with or without PVD, compared to non-smoking controls; and in patients with COPD and PVD compared to smoking controls. PWV was higher in COPD with PVD patients compared to both non-smoking and smoking controls in a model adjusted by age and the Framingham score; PWV was also higher in patients with COPD and PVD compared to COPD without PVD patients in the non-adjusted analysis. FMD and PWV correlated significantly with forced expiratory volume in the first second (FEV1), diffusing capacity for carbon monoxide (DLCO) and systolic PAP. FMD and PWV were correlated in all subjects.Discussion: We conclude that endothelial dysfunction of systemic arteries is common in COPD, irrespective if they have PVD or not. COPD patients with PVD show increased stiffness and greater impairment of endothelial function in systemic arteries. These findings suggest the association of vascular impairment in both pulmonary and systemic territories in a subset of COPD patients.Keywords: COPD, pulmonary circulation and pulmonary hypertension, emphysema, cardiovascular diseases
- Published
- 2020
6. Updated Perspectives on Pulmonary Hypertension in COPD
- Author
-
Blanco I, Tura-Ceide O, Peinado VI, and Barberà JA
- Subjects
chronic lung disease ,pulmonary circulation ,vascular remodeling ,pulmonary arterial pressure. ,Diseases of the respiratory system ,RC705-779 - Abstract
Isabel Blanco,1,2 Olga Tura-Ceide,1,2 Victor Ivo Peinado,1,2 Joan Albert Barberà1,2 1Department of Pulmonary Medicine, Hospital Clínic-Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain; 2Biomedical Research Networking Center on Respiratory Diseases (CIBERES), Madrid, SpainCorrespondence: Joan Albert BarberàDepartment of Pulmonary Medicine, Hospital Clínic, Villarroel 170, Barcelona 08036, SpainTel +34-9322757Email jbarbera@clinic.catAbstract: Pulmonary hypertension (PH) is a frequent and important complication of chronic obstructive pulmonary disease (COPD). It is associated with worse clinical courses with more frequent exacerbation episodes, shorter survival, and greater need of health resources. PH is usually of moderate severity and progresses slowly, without altering right ventricular function in the majority of cases. Nevertheless, a reduced subgroup of patients may present disproportionate PH, with pulmonary artery pressure (PAP) largely exceeding the severity of respiratory impairment. These patients may represent a group with an exaggerated vascular impairment (pulmonary vascular phenotype) to factors that induce PH in COPD or be patients in whom idiopathic pulmonary arterial hypertension (PAH) coexist. The present review addresses the current definition and classification of PH in COPD, the distinction among the different phenotypes of pulmonary vascular disease that might present in COPD patients, and the therapeutic approach to PH in COPD based on the available scientific evidence.Keywords: chronic lung disease, pulmonary circulation, vascular remodeling, pulmonary arterial pressure
- Published
- 2020
7. Post-COVID-19 Patients Show Vascular Sequelae That Last Up to 6 Months
- Author
-
Poyatos, P., primary, Luque, N., additional, Eizaguirre, S., additional, Belda, S., additional, Bonnin, M., additional, Sánchez, M., additional, Peracaula, M., additional, Orriols, R., additional, and Tura-Ceide, O., additional
- Published
- 2023
- Full Text
- View/download PDF
8. Post-COVID-19 patients show vascular sequelae that last up to 6 months
- Author
-
Poyatos, P, primary, Luque, N, additional, Eizaguirre, S, additional, Belda, S, additional, Bonnin, M, additional, Sánchez, M, additional, Peracaula, M, additional, Orriols, R, additional, and Tura-Ceide, O, additional
- Published
- 2023
- Full Text
- View/download PDF
9. Predictors of the response to combined therapy with phosphodiesterase-5 inhibitors and endothelin receptor antagonists in pulmonary arterial hypertension
- Author
-
GARCIA, A R, primary, Blanco, I, additional, Lopez Meseguer, M, additional, Domingo Morera, J A, additional, Martin Ontiyuelo, C, additional, Tura Ceide, O, additional, Otero Gonzalez, I, additional, Escribano Subías, P, additional, and Albert Barberà, J, additional
- Published
- 2022
- Full Text
- View/download PDF
10. Post-COVID-19 patients show vascular sequelae that last up to 6 months
- Author
-
Poyatos, P, primary, Luque, N, additional, Eizaguirre, S, additional, Belda, S, additional, Bonnin, M, additional, Sánchez, M, additional, Peracaula, M, additional, Orriols, R, additional, and Tura-Ceide, O, additional
- Published
- 2022
- Full Text
- View/download PDF
11. Peripheral Endothelial Dysfunction and Arterial Stiffness in Pulmonary Arterial Hypertension: Association with Severity and Changes After Treatment
- Author
-
Garcia, A.R., primary, Blanco, I., additional, Torralba-Garcia, Y., additional, Martin Ontiyuelo, C., additional, Piccari, L., additional, Peinado, V., additional, Ramirez, A.M., additional, Tura-Ceide, O., additional, and Barbera, J.A., additional
- Published
- 2022
- Full Text
- View/download PDF
12. VP42.11: Influence of activated complement and coagulation cascades on endothelial cell dysfunction in early onset pre‐eclampsia
- Author
-
Youssef, L., primary, Palomo, M., additional, Torramade‐Moix, S., additional, Blasco, M., additional, Crovetto, F., additional, Garcia, H., additional, Tura‐Ceide, O., additional, Dantas, A., additional, Campistol, J., additional, Garcia‐Pagan, J., additional, Gratacos, E., additional, Diaz‐Ricart, M., additional, and Crispi, F., additional
- Published
- 2021
- Full Text
- View/download PDF
13. OC07.11: Metabolomic profiling of pathophysiological pathways in early onset severe pre‐eclampsia
- Author
-
Youssef, L., primary, Garcia, H., additional, Tura‐Ceide, O., additional, Dantas, A., additional, Canela, N., additional, Campistol, J., additional, Garcia‐Pagan, J., additional, Diaz‐Ricart, M., additional, Gratacós, E., additional, and Crispi, F., additional
- Published
- 2020
- Full Text
- View/download PDF
14. The Activated Pulmonary Endothelium of Chronic Thromboembolic Pulmonary Hypertension Patients Exhibits Elevated Platelet Adhesion
- Author
-
Manz, X.D., primary, Pan, X., additional, Symersky, P., additional, Majolée, J., additional, Tura-Ceide, O., additional, Hordijk, P., additional, Voorberg, J., additional, Bogaard, H.J., additional, and Szulcek, R., additional
- Published
- 2020
- Full Text
- View/download PDF
15. Comparison of metabolic profile in endothelial cells of chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension
- Author
-
Rodríguez, C, primary, Smolders, V F, additional, Blanco, I, additional, Szulcek, R, additional, Quax, P H, additional, Piccari, L, additional, Bonjoch, C, additional, Hu, X, additional, Sebastián, L, additional, Castellà, M, additional, Osorio, J, additional, Cascante, M, additional, Peinado, V I, additional, Barberà, J A, additional, and Tura-Ceide, O, additional
- Published
- 2020
- Full Text
- View/download PDF
16. Analysis of Wnt pathway genes during ex vivo expansion and neutrophil differentiation of umbilical cord-blood derived CD34+ cells
- Author
-
Gallagher, R. C. J., Tura-Ceide, O., Turner, M., and Barclay, R.
- Published
- 2010
- Full Text
- View/download PDF
17. Influence of menstrual cycle on circulating endothelial progenitor cells
- Author
-
Robb, A.O., Mills, N.L., Smith, I.B.J., Short, A., Tura-Ceide, O., Barclay, G.R., Blomberg, A., Critchley, H.O.D., Newby, D.E., and Denison, F.C.
- Published
- 2009
18. Survivin Inhibition as a Potential Target for Pulmonary Arterial Hypertension
- Author
-
Blanco, I., primary, Marquina, M., additional, Tura-Ceide, O., additional, Peinado, V.I., additional, and Barbera, J.A., additional
- Published
- 2019
- Full Text
- View/download PDF
19. Identification of the origin of circulating endothelial progenitor cells
- Author
-
Fujisawa, T., primary, Brittan, M., additional, Tura-Ceide, O., additional, Hunter, A., additional, Mitchell, A., additional, Vesey, A., additional, Skinner, E.M., additional, Medine, C., additional, Gallogly, S., additional, Hadoke, P.W.F., additional, Keith, C., additional, Sproul, A., additional, Roddie, H., additional, McQuaker, G., additional, Wilmut, I., additional, and Mills, N.L., additional
- Published
- 2015
- Full Text
- View/download PDF
20. Analysis of Wnt pathway genes duringex vivoexpansion and neutrophil differentiation of umbilical cord-blood derived CD34+cells
- Author
-
Gallagher, R. C. J., primary, Tura-Ceide, O., additional, Turner, M., additional, and Barclay, R., additional
- Published
- 2010
- Full Text
- View/download PDF
21. Influence of menstrual cycle on circulating endothelial progenitor cells
- Author
-
Robb, A.O., primary, Mills, N.L., additional, Smith, I.B.J., additional, Short, A., additional, Tura-Ceide, O., additional, Barclay, G.R., additional, Blomberg, A., additional, Critchley, H.O.D., additional, Newby, D.E., additional, and Denison, F.C., additional
- Published
- 2008
- Full Text
- View/download PDF
22. Analysis of Wnt pathway genes during ex vivo expansion and neutrophil differentiation of umbilical cord-blood derived CD34+ cells.
- Author
-
Gallagher, R. C. J., Tura-Ceide, O., Turner, M., and Barclay, R.
- Subjects
- *
NEUTROPHILS , *UMBILICAL cord , *GENE expression , *CELLS , *GENETIC regulation , *CORD blood - Abstract
Previous work has shown that optimal ex vivo expansion and differentiation of CD34+ progenitor cells into neutrophils is by addition of Flt3-L, SCF and G-CSF. Here we report that a variety of genes involved in the WNT pathway are transcriptionally active in both undifferentiated and differentiated umbilical cord blood CD34+ cells, however statistically significant changes in gene expression are not always consistent across UCB samples. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
23. Linking in vitro models of endothelial dysfunction with cell senescence
- Author
-
Àngela Vea Badenes, Manel Sabaté Tenas, Joaquim Bobi Gibert, Francisco R. Jimenez Trinidad, Ana Paula Dantas, Marta Arrieta Ruiz, Montserrat Rigol Muxart, Antoni Valera Cañellas, Mercè Roqué Moreno, Olga Tura-Ceide, Xavier Freixa Rofastes, Núria Solanes Batlló, Cardiology, Institut Català de la Salut, [Jimenez Trinidad FR, Arrieta Ruiz M, Solanes Batlló N, Valera Cañellas A, Roqué Moreno M, Freixa Rofastes X, Sabaté Tenas M, Dantas AP] Cardiology Department, Institute Clinic Cardiovascular (ICCV), Hospital Clinic, Institute d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain. [Vea Badenes A] Department of Pulmonary Medicine, Servei de Pneumologia, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain. [Bobi Gibert J] Department of Cardiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. [Tura-Ceide O] Department of Pulmonary Medicine, Servei de Pneumologia, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain. Biomedical Research Networking Centre on Respiratory Diseases (CIBERES), CB06/06/0011 Group, Pulmonary Hypertension Programme, Instituto de Salud Carlos III, Madrid, Spain. Department of Pulmonary Medicine, Santa Caterina Hospital de Salt, Biomedical Research Institute (IDIBGI), Hospital Universitari de Girona Doctor Josep Trueta, Institut Català de la Salut (ICS), Girona, Spain. [Rigol Muxart M] Cardiology Department, Institute Clinic Cardiovascular (ICCV), Hospital Clinic, Institute d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain, and Hospital Universitari de Girona Dr Josep Trueta
- Subjects
Senescence ,senescence ,Science ,Cell ,Cell Physiological Phenomena::Cellular Senescence [PHENOMENA AND PROCESSES] ,Pharmacology ,Biology ,medicine.disease_cause ,Endoteli ,células::células epiteliales::células endoteliales [ANATOMÍA] ,Article ,General Biochemistry, Genetics and Molecular Biology ,Umbilical vein ,endothelial dysfunction ,SDG 3 - Good Health and Well-being ,medicine ,oxidative stress ,Endothelial dysfunction ,Ecology, Evolution, Behavior and Systematics ,in vitro models ,Cells::Epithelial Cells::Endothelial Cells [ANATOMY] ,cell culture ,starvation ,Paleontology ,medicine.disease ,Endothelial stem cell ,medicine.anatomical_structure ,Space and Planetary Science ,Cell culture ,Toxicity ,fenómenos fisiológicos celulares::senescencia celular [FENÓMENOS Y PROCESOS] ,Cèl·lules - Envelliment ,Oxidative stress - Abstract
Disfunció endotelial; Envellliment cel·lular Disfunción endotelial; Envejecimiento celular Endothelial dysfunction; Senescence Endothelial cell dysfunction is the principal cause of several cardiovascular diseases that are increasing in prevalence, healthcare costs, and mortality. Developing a standardized, representative in vitro model of endothelial cell dysfunction is fundamental to a greater understanding of the pathophysiology, and to aiding the development of novel pharmacological therapies. We subjected human umbilical vein endothelial cells (HUVECs) to different periods of nutrient deprivation or increasing doses of H2O2 to represent starvation or elevated oxidative stress, respectively, to investigate changes in cellular function. Both in vitro cellular models of endothelial cell dysfunction-associated senescence developed in this study, starvation and oxidative stress, were validated by markers of cellular senescence (increase in β-galactosidase activity, and changes in senescence gene markers SIRT1 and P21) and endothelial dysfunction as denoted by reductions in angiogenic and migratory capabilities. HUVECs showed a significant H2O2 concentration-dependent reduction in cell viability (p < 0.0001), and a significant increase in oxidative stress (p < 0.0001). Furthermore, HUVECs subjected to 96 h of starvation, or exposed to concentrations of H2O2 of 400 to 1000 μM resulted in impaired angiogenic and migratory potentials. These models will enable improved physiological studies of endothelial cell dysfunction, and the rapid testing of cellular efficacy and toxicity of future novel therapeutic compounds. This research was funded by Beca de Investigacion Basica en Cardiologia from the Sociedad Española de Cardiologia, Fondo de Investigacion en Salud (grants PI18/00277, PI16/00742, PI19/00264, PI18/00960 and PI15/00553) from the Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III–Fondo Europeo de Desarrollo Regional (FEDER), and Spanish Society of Respiratory Medicine (SEPAR) and Catalan Society of Pneumology (SOCAP) grants. FRJT and OTC are the recipients of the Ayudas para la formación de profesorado universitario (FPU19/04925) and Miguel Servet (CP17/00114) grants, respectively, from the Spanish Ministry of Science and Innovation. IDIBAPS belongs to the CERCA Programme, and receives partial funding from the Generalitat de Catalunya. Cofunding was provided by the Fondo Europeo de Desarrollo Regional (FEDER); “Una manera de hacer Europa”.
- Published
- 2021
24. Circulating Cell Biomarkers in Pulmonary Arterial Hypertension: Relationship with Clinical Heterogeneity and Therapeutic Response
- Author
-
Isabel Crespo, Manuel López-Meseguer, Jéssica García-Lucio, Joan Albert Barberà, Elisabet Ferrer, Isabel Blanco, Victor I. Peinado, Roberto Del Pozo, Carmen Pilar Simeón-Aznar, Clara Martín-Ontiyuelo, Agustin Roberto Garcia, Diego A Rodríguez-Chiaradía, Olga Tura-Ceide, Institut Català de la Salut, [Tura-Ceide O] Department of Pulmonary Medicine, Hospital Clínic-Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Spain. Biomedical Research Networking Centre on Respiratory Diseases (CIBERES), 28029 Madrid, Spain. Girona Biomedical Research Institute (IDIBGI), 17190 Girona, Spain. [Blanco I] Department of Pulmonary Medicine, Hospital Clínic-Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Spain. Biomedical Research Networking Centre on Respiratory Diseases (CIBERES), 28029 Madrid, Spain. [Garcia-Lucio J, Del Pozo R, García AR, Ferrer E] Department of Pulmonary Medicine, Hospital Clínic-Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Spain. [Simeon-Aznar CP] Unitat de Malalties Autoimmunes Sistèmiques, Servei de Medicina Interna, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain. [López-Meseguer M] Servei de Pneumologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain, and Vall d'Hebron Barcelona Hospital Campus
- Subjects
Male ,CD31 ,endothelial extracellular vesicles ,medicine.medical_treatment ,CD34 ,Hipertensió pulmonar - Tractament ,030204 cardiovascular system & hematology ,Respiratory Tract Diseases::Lung Diseases::Hypertension, Pulmonary::Familial Primary Pulmonary Hypertension [DISEASES] ,Gastroenterology ,Scleroderma ,factores biológicos::biomarcadores [COMPUESTOS QUÍMICOS Y DROGAS] ,endothelial dysfunction ,Targeted therapy ,0302 clinical medicine ,Cell-Derived Microparticles ,pulmonary arterial hypertension ,polycyclic compounds ,Biology (General) ,Endothelial dysfunction ,Otros calificadores::Otros calificadores::/metabolismo [Otros calificadores] ,Hipertensió pulmonar ,Stem Cells ,Biochemical markers ,Other subheadings::Other subheadings::/metabolism [Other subheadings] ,General Medicine ,progenitor cells ,Middle Aged ,Treatment Outcome ,medicine.anatomical_structure ,Marcadors bioquímics ,Portal hypertension ,Female ,PAH-specific treatment ,medicine.medical_specialty ,QH301-705.5 ,Connective tissue ,Biological Factors::Biomarkers [CHEMICALS AND DRUGS] ,células::células epiteliales::células endoteliales [ANATOMÍA] ,Article ,Pulmonary hypertension ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,Progenitor cell ,Cells::Epithelial Cells::Endothelial Cells [ANATOMY] ,business.industry ,Hemodynamics ,Endothelial Cells ,biomarkers ,medicine.disease ,030228 respiratory system ,enfermedades respiratorias::enfermedades pulmonares::hipertensión pulmonar::hipertensión pulmonar primaria familiar [ENFERMEDADES] ,Case-Control Studies ,business - Abstract
Biomarcadores; Disfunción endotelial; Células progenitoras Biomarcadors; Disfunció endotelial; Cèl·lules progenitores Biomarkers; Endothelial dysfunction; Progenitor cells Background: Endothelial dysfunction is central to PAH. In this study, we simultaneously analysed circulating levels of endothelial microvesicles (EMVs) and progenitor cells (PCs) in PAH and in controls, as biomarkers of pulmonary endothelial integrity and evaluated differences among PAH subtypes and as a response to treatment. Methods: Forty-seven controls and 144 patients with PAH (52 idiopathic, 9 heritable, 31 associated with systemic sclerosis, 15 associated with other connective tissue diseases, 20 associated with HIV and 17 associated with portal hypertension) were evaluated. Forty-four patients with scleroderma and 22 with HIV infection, but without PAH, were also studied. Circulating levels of EMVs, total (CD31+CD42b−) and activated (CD31+CD42b−CD62E+), as well as circulating PCs (CD34+CD133+CD45low) were measured by flow cytometry and the EMVs/PCs ratio was computed. In treatment-naïve patients, measurements were repeated after 3 months of PAH therapy. Results: Patients with PAH showed higher numbers of EMVs and a lower percentage of PCs, compared with healthy controls. The EMV/PC ratio was increased in PAH patients, and in patients with SSc or HIV without PAH. After starting PAH therapy, individual changes in EMVs and PCs were variable, without significant differences being observed as a group. Conclusion: PAH patients present disturbed vascular homeostasis, reflected in changes in circulating EMV and PC levels, which are not restored with PAH targeted therapy. Combined measurement of circulating EMVs and PCs could be foreseen as a potential biomarker of endothelial dysfunction in PAH. This research was funded by grants PI12/00510, PI15/00582 and PI18/00960 from the Institute of Health Carlos III (ISCiii), Spain, co-funded by the European Union (ERDF/ESF); the Catalan Society of Respiratory Medicine (SOCAP); and the Fundación Contra la Hipertensión Pulmonar (FCHP). OTC is the former recipient of a Marie Curie Post-Doctoral Fellowship Award BIOTRACK-IDIBAPS, and the current recipient of a Miguel Servet contract from ISCiii (CP17/00114).
- Published
- 2021
- Full Text
- View/download PDF
25. Functional and metabolic characterization of endothelial cells in chronic thromboembolic pulmonary hypertension
- Author
-
Smolders, V.F.E.D., Quax, P.H.A., Cascante, M., Tura-Ceide, O., Goumans, M.J.T.H., Jukema, J.W., Bogaard, H.J., Hoefer, I., and Leiden University
- Subjects
Inflammation ,Cell Culture ,Cardiovascular pathology ,Chronic thromboembolic pulmonary hypertension ,Thrombosis ,Patient-derived cells ,Cell Metabolism - Abstract
Pulmonary hypertension (PH) is a condition of increased blood pressure within the arteries of the lung (mPAP > 20mmHg) which affects approximately 1% of the global population. Chronic thromboembolic pulmonary hypertension (CTEPH), group 4 PH, is characterized by unresolved pulmonary emboli and pulmonary vascular remodeling of both occluded and non-occluded vessels. The general aim of this thesis was to improve the understanding of CTEPH pathophysiology by focusing on patient endothelial cell (EC) behaviour and function. For this purpose, we isolated ECs from vascular material collected at pulmonary endarterectomy in patients with CTEPH (referred to as CTEPH-EC) and validated them as an in vitro model for studying endothelial pathology in CTEPH. In conclusion, we identified several abnormalities in CTEPH-EC that could play a role in pathological mechanisms driving CTEPH-specific vascular changes. We described alterations in key processes such as angiogenesis and migration, oxidative stress, metabolism and inflammation. Each of these processes may represent targets for novel therapies or biomarkers.
- Published
- 2020
26. Clinical physiology and sleep: insights from the European Respiratory Society Congress 2017
- Author
-
Maria R. Bonsignore, Olga Tura-Ceide, Isaac Almendros, Andrea Crespo, Almendros I., Crespo A., Tura-Ceide O., and Bonsignore M.R.
- Subjects
Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,business.industry ,education ,MEDLINE ,Physiology ,social sciences ,Review Article ,Settore MED/10 - Malattie Dell'Apparato Respiratorio ,Sleep in non-human animals ,Clinical Physiology ,medicine ,Respiratory system ,Intensive care medicine ,business ,health care economics and organizations ,sleep, clinical physiology, cancer - Abstract
The 2017 Annual Congress of the European Respiratory Society (ERS) held in Milan has featured the latest research on clinical physiology and sleep.
- Published
- 2017
27. Endothelial dysfunction and cardiovascular risk in post-COVID-19 patients after 6- and 12-months SARS-CoV-2 infection.
- Author
-
Poyatos P, Luque N, Sabater G, Eizaguirre S, Bonnin M, Orriols R, and Tura-Ceide O
- Subjects
- Humans, Male, Female, Middle Aged, Endothelium, Vascular physiopathology, Aged, Adult, Biomarkers blood, Endothelial Progenitor Cells, Case-Control Studies, Post-Acute COVID-19 Syndrome, COVID-19 complications, COVID-19 physiopathology, COVID-19 blood, Cardiovascular Diseases epidemiology, Cardiovascular Diseases etiology, SARS-CoV-2
- Abstract
Introduction: SARS-CoV-2 infection causes severe endothelial damage, an essential step for cardiovascular complications. Endothelial-colony forming cells (ECFCs) act as a biomarker of vascular damage but their role in SARS-CoV-2 remain unclear. The aim of this study was to assess whether the number of ECFCs and angiogenic biomarkers remained altered after 6 and 12-months post-infection and whether this imbalance correlated with the presence of long-COVID syndrome and other biological parameters measured., Methods: Seventy-two patients were recruited at different time-points after overcoming COVID-19 and thirty-one healthy controls. All subjects were matched for age, gender, BMI, and comorbidities. ECFCs were obtained from peripheral blood and cultured with specific conditions., Results: The results confirm the presence of a long-term sequela in post-COVID-19 patients, with an abnormal increase in ECFC production compared to controls (82.8% vs. 48.4%, P < 0.01) that is maintained up to 6-months (87.0% vs. 48.4%, P < 0.01) and 12-months post-infection (85.0% vs. 48.4%, P < 0.01). Interestingly, post-COVID-19 patients showed a significant downregulation of angiogenesis-related proteins compared to controls indicating a clear endothelial injury. Troponin, NT-proBNP and ferritin levels, markers of cardiovascular risk and inflammation, remained elevated up to 12-months post-infection. Patients with lower numbers of ECFC exhibited higher levels of inflammatory markers, such as ferritin, suggesting that ECFCs may play a protective role. Additionally, long-COVID syndrome was associated with higher ferritin levels and with female gender., Conclusions: These findings highlight the presence of vascular sequela that last up to 6- and 12-months post-infection and point out the need for preventive measures and patient follow-up., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
28. Pharmacological modulation of vascular ageing: A review from VascAgeNet.
- Author
-
Roth L, Dogan S, Tuna BG, Aranyi T, Benitez S, Borrell-Pages M, Bozaykut P, De Meyer GRY, Duca L, Durmus N, Fonseca D, Fraenkel E, Gillery P, Giudici A, Jaisson S, Johansson M, Julve J, Lucas-Herald AK, Martinet W, Maurice P, McDonnell BJ, Ozbek EN, Pucci G, Pugh CJA, Rochfort KD, Roks AJM, Rotllan N, Shadiow J, Sohrabi Y, Spronck B, Szeri F, Terentes-Printzios D, Tunc Aydin E, Tura-Ceide O, Ucar E, and Yetik-Anacak G
- Subjects
- Humans, Oxidative Stress, Cellular Senescence, Signal Transduction, Aging metabolism, Vascular Stiffness
- Abstract
Vascular ageing, characterized by structural and functional changes in blood vessels of which arterial stiffness and endothelial dysfunction are key components, is associated with increased risk of cardiovascular and other age-related diseases. As the global population continues to age, understanding the underlying mechanisms and developing effective therapeutic interventions to mitigate vascular ageing becomes crucial for improving cardiovascular health outcomes. Therefore, this review provides an overview of the current knowledge on pharmacological modulation of vascular ageing, highlighting key strategies and promising therapeutic targets. Several molecular pathways have been identified as central players in vascular ageing, including oxidative stress and inflammation, the renin-angiotensin-aldosterone system, cellular senescence, macroautophagy, extracellular matrix remodelling, calcification, and gasotransmitter-related signalling. Pharmacological and dietary interventions targeting these pathways have shown potential in ameliorating age-related vascular changes. Nevertheless, the development and application of drugs targeting vascular ageing is complicated by various inherent challenges and limitations, such as certain preclinical methodological considerations, interactions with exercise training and sex/gender-related differences, which should be taken into account. Overall, pharmacological modulation of endothelial dysfunction and arterial stiffness as hallmarks of vascular ageing, holds great promise for improving cardiovascular health in the ageing population. Nonetheless, further research is needed to fully elucidate the underlying mechanisms and optimize the efficacy and safety of these interventions for clinical translation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
29. Autonomous metabolic reprogramming and oxidative stress characterize endothelial dysfunction in acute myocardial infarction.
- Author
-
Zodda E, Tura-Ceide O, Mills NL, Tarragó-Celada J, Carini M, Thomson TM, and Cascante M
- Subjects
- Humans, Reactive Oxygen Species metabolism, Metabolic Reprogramming, Oxidative Stress, Glycolysis, Glutathione metabolism, Phosphofructokinase-2 metabolism, Endothelial Cells metabolism, Myocardial Infarction
- Abstract
Compelling evidence has accumulated on the role of oxidative stress on the endothelial cell (EC) dysfunction in acute coronary syndrome. Unveiling the underlying metabolic determinants has been hampered by the scarcity of appropriate cell models to address cell-autonomous mechanisms of EC dysfunction. We have generated endothelial cells derived from thrombectomy specimens from patients affected with acute myocardial infarction (AMI) and conducted phenotypical and metabolic characterizations. AMI-derived endothelial cells (AMIECs) display impaired growth, migration, and tubulogenesis. Metabolically, AMIECs displayed augmented ROS and glutathione intracellular content, with a diminished glucose consumption coupled to high lactate production. In AMIECs, while PFKFB3 protein levels of were downregulated, PFKFB4 levels were upregulated, suggesting a shunting of glycolysis towards the pentose phosphate pathway, supported by upregulation of G6PD. Furthermore, the glutaminolytic enzyme GLS was upregulated in AMIECs, providing an explanation for the increase in glutathione content. Finally, AMIECs displayed a significantly higher mitochondrial membrane potential than control ECs, which, together with high ROS levels, suggests a coupled mitochondrial activity. We suggest that high mitochondrial proton coupling underlies the high production of ROS, balanced by PPP- and glutaminolysis-driven synthesis of glutathione, as a primary, cell-autonomous abnormality driving EC dysfunction in AMI., Competing Interests: EZ, OT, NM, JT, MC, TT, MC No competing interests declared, (© 2023, Zodda et al.)
- Published
- 2023
- Full Text
- View/download PDF
30. Predictors of the response to phosphodiesterase-5 inhibitors in pulmonary arterial hypertension: an analysis of the Spanish registry.
- Author
-
Garcia AR, Blanco I, Ramon L, Pérez-Sagredo J, Guerra-Ramos FJ, Martín-Ontiyuelo C, Tura-Ceide O, Pastor-Pérez F, Escribano-Subías P, and Barberà JA
- Subjects
- Humans, Male, Cyclic Nucleotide Phosphodiesterases, Type 5, Phosphodiesterase 5 Inhibitors therapeutic use, Familial Primary Pulmonary Hypertension, Registries, Pulmonary Arterial Hypertension diagnosis, Pulmonary Arterial Hypertension drug therapy, Pulmonary Arterial Hypertension epidemiology, HIV Infections
- Abstract
Background: Achieving and maintaining a low-risk profile is associated with favorable outcome in pulmonary arterial hypertension (PAH). The effects of treatment on risk profile are variable among patients., Objective: To Identify variables that might predict the response to treatment with phosphodiesterase-5 inhibitors (PDE-5i) in PAH., Methods: We carried out a cohort analysis of the Spanish PAH registry in 830 patients diagnosed with PAH that started PDE5i treatment and had > 1 year follow-up. 644 patients started PDE-5i either in mono- or add-on therapy and 186 started combined treatment with PDE-5i and endothelin receptor antagonist (ERA). Responders were considered when at 1 year they: (1) were alive; (2) did not present clinical worsening; and (3) improved European Society of Cardiology/European Respiratory Society (ESC/ERS) risk score or remained in low-risk. Univariate and multivariate logistic regression models were used to analyze variables associated with a favorable response., Results: Two hundred and ten patients (33%) starting PDE-5i alone were classified as responders, irrespective of whether it was mono- or add-on therapy. In addition to known predictors of PAH outcome (low-risk at baseline, younger age), male sex and diagnosis of portopulmonary hypertension (PoPH) or HIV-PAH were independent predictors of favorable response to PDE-5i. Diffusing capacity for carbon monoxide (DLco) ≤ 40% of predicted was associated with an unfavorable response. When PDE-5i were used in upfront combination, 58% of patients were responders. In this group, diagnosis of idiopathic PAH (IPAH) was an independent predictor of favorable response, whereas connective tissue disease-PAH was associated with an unfavorable response., Conclusion: Male sex and diagnosis of PoPH or HIV-PAH are predictors of favorable effect of PDE-5i on risk profile when used as mono- or add-on therapy. Patients with IPAH respond more favorably to PDE-5i when used in upfront combination. These results identify patient profiles that may respond favorably to PDE-5i in monotherapy and those who might benefit from alternative treatment strategies., (© 2023. BioMed Central Ltd., part of Springer Nature.)
- Published
- 2023
- Full Text
- View/download PDF
31. Effects of Exercise Training on Circulating Biomarkers of Endothelial Function in Pulmonary Arterial Hypertension.
- Author
-
Rodríguez-Chiaradía DA, Khilzi K, Blanco I, Rodó-Pin A, Martin-Ontiyuelo C, Herranz Blasco A, Garcia-Lucio J, Molina L, Marco E, Barreiro E, Piccari L, Peinado VI, Garcia AR, Tura-Ceide O, and Barberà JA
- Abstract
Introduction: In stable patients with pulmonary arterial hypertension (PAH), pulmonary rehabilitation (PR) is an effective, safe and cost-effective non-pharmacological treatment. However, the effects of PR on vascular function have been poorly explored. This study aimed to compare the amounts of circulating progenitor cells (PCs) and endothelial microvesicles (EMVs) in patients with PAH before and after 8 weeks of endurance exercise training as markers of vascular competence., Methods: A prospective study of 10 consecutive patients with PAH that successfully finished a PR program (8 weeks) was carried out before and after this intervention. Levels of circulating PCs defined as CD34+CD45low progenitor cells and levels of EMVs (CD31+ CD42b-) were measured by flow cytometry. The ratio of PCs to EMVs was taken as a measure of the balance between endothelial damage and repair capacity., Results: All patients showed training-induced increases in endurance time (mean change 287 s). After PR, the number of PCs (CD34+CD45low/total lymphocytes) was increased ( p < 0.05). In contrast, after training, the level of EMVs (CD31+ CD42b-/total EMVs) was reduced. The ratio of PCs to EMVs was significantly higher after training ( p < 0.05)., Conclusion: Our study shows, for the first time, that endurance exercise training in patients with stable PAH has a positive effect, promoting potential mechanisms of damage/repair in favor of repair. This effect could contribute to a positive hemodynamic and clinical response.
- Published
- 2023
- Full Text
- View/download PDF
32. Atrophy signaling pathways in respiratory and limb muscles of guinea pigs exposed to chronic cigarette smoke: role of soluble guanylate cyclase stimulation.
- Author
-
Peinado VI, Guitart M, Blanco I, Tura-Ceide O, Paul T, Barberà JA, and Barreiro E
- Subjects
- Guinea Pigs, Animals, Soluble Guanylyl Cyclase metabolism, Guanylate Cyclase metabolism, Muscle, Skeletal metabolism, Signal Transduction, Biomarkers metabolism, Atrophy metabolism, Atrophy pathology, Cigarette Smoking, Pulmonary Disease, Chronic Obstructive pathology
- Abstract
Skeletal muscle dysfunction in chronic obstructive pulmonary disease (COPD) is characterized by a significant reduction in muscle strength and endurance. Preclinical studies show that stimulation of the soluble guanylate cyclase (sGC)-cGMP pathway attenuates muscle mass loss and prevents cigarette smoke-induced oxidative stress, indicating that pharmacological activation of the guanylyl cyclase pathway in COPD may provide a beneficial therapeutic strategy that reaches beyond the lung. In this study, conducted in an animal model of COPD, we first set out to assess the effect of cigarette smoke (CS) on biomarkers of muscle fatigue, such as protein degradation and its transcriptional regulation, in two types of muscles with different energy demands, i.e., the diaphragm and the gastrocnemius muscle of the limbs. Second, we evaluated the administration of an sGC stimulator on these markers to study the potential efficacy of such treatment in the recovery of skeletal muscle function. Exposure to CS led to weight loss, which was associated in the gastrocnemius with increased levels of proteolytic markers of muscle atrophy (MURF-1, Atrogin-1, proteasome C8 subunit 20 s, and total protein ubiquitination), whereas the size of fast-twitch muscle fibers decreased significantly. Long-term treatment with the sGC stimulator BAY 41-2272 resulted in a significant reduction in gastrocnemius levels of the aforementioned proteolytic markers, concomitant with a weight recovery and increased cGMP levels. Remarkably, levels of some of the analyzed biomarkers differed between respiratory and limb muscles. In conclusion, targeting sGC might exert beneficial effects on muscle alterations in patients with COPD.
- Published
- 2023
- Full Text
- View/download PDF
33. Oxidative Stress and Antioxidant Therapy in Pulmonary Hypertension.
- Author
-
Poyatos P, Gratacós M, Samuel K, Orriols R, and Tura-Ceide O
- Abstract
Pulmonary hypertension (PH) is a progressive disease characterized by elevated artery pressures and pulmonary vascular resistance. Underlying mechanisms comprise endothelial dysfunction, pulmonary artery remodeling and vasoconstriction. Several studies have shown evidence of the critical role of oxidative stress in PH pathophysiology. Alteration of redox homeostasis produces excessive generation of reactive oxygen species, inducing oxidative stress and the subsequent alteration of biological molecules. Exacerbations in oxidative stress production can lead to alterations in nitric oxide signaling pathways, contributing to the proliferation of pulmonary arterial endothelial cells and smooth muscle cells, inducing PH development. Recently, antioxidant therapy has been suggested as a novel therapeutic strategy for PH pathology. However, the favorable outcomes observed in preclinical studies have not been consistently reproduced in clinical practice. Therefore, targeting oxidative stress as a therapeutic intervention for PH is an area that is still being explored. This review summarizes the contribution of oxidative stress to the pathogenesis of the different types of PH and suggests antioxidant therapy as a promising strategy for PH treatment.
- Published
- 2023
- Full Text
- View/download PDF
34. Survivin inhibition with YM155 ameliorates experimental pulmonary arterial hypertension.
- Author
-
Blanco I, Marquina M, Tura-Ceide O, Ferrer E, Ramírez AM, Lopez-Meseguer M, Callejo M, Perez-Vizcaino F, Peinado VI, and Barberà JA
- Abstract
Background: Imbalance between cell proliferation and apoptosis underlies the development of pulmonary arterial hypertension (PAH). Current vasodilator treatment of PAH does not target the uncontrolled proliferative process in pulmonary arteries. Proteins involved in the apoptosis pathway may play a role in PAH and their inhibition might represent a potential therapeutic target. Survivin is a member of the apoptosis inhibitor protein family involved in cell proliferation. Objectives: This study aimed to explore the potential role of survivin in the pathogenesis of PAH and the effects of its inhibition. Methods: In SU5416/hypoxia-induced PAH mice we assessed the expression of survivin by immunohistochemistry, western-blot analysis, and RT-PCR; the expression of proliferation-related genes (Bcl2 and Mki67); and the effects of the survivin inhibitor YM155. In explanted lungs from patients with PAH we assessed the expression of survivin, BCL2 and MKI67. Results: SU5416/hypoxia mice showed increased expression of survivin in pulmonary arteries and lung tissue extract, and upregulation of survivin, Bcl2 and Mki67 genes. Treatment with YM155 reduced right ventricle (RV) systolic pressure, RV thickness, pulmonary vascular remodeling, and the expression of survivin, Bcl2, and Mki67 to values similar to those in control animals. Lungs of patients with PAH also showed increased expression of survivin in pulmonary arteries and lung extract, and also that of BCL2 and MKI67 genes, compared with control lungs. Conclusion: We conclude that survivin might be involved in the pathogenesis of PAH and that its inhibition with YM155 might represent a novel therapeutic approach that warrants further evaluation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Blanco, Marquina, Tura-Ceide, Ferrer, Ramírez, Lopez-Meseguer, Callejo, Perez-Vizcaino, Peinado and Barberà.)
- Published
- 2023
- Full Text
- View/download PDF
35. Artificial Stone Silicosis. Progression and Laboral Impact After 3-years Follow-up.
- Author
-
Orriols R, Torrente A, Campà MT, Comas-Cufí M, Tura-Ceide O, Sabater G, and Vendrell M
- Subjects
- Humans, Follow-Up Studies, Silicon Dioxide, Silicosis complications, Occupational Diseases etiology, Occupational Diseases therapy, Occupational Exposure adverse effects
- Published
- 2023
- Full Text
- View/download PDF
36. Editorial: Metabolic changes in vascular disorders: A path for early diagnosis and new therapeutic targets.
- Author
-
Ayyoub S, Blanco I, Izquierdo-García JL, and Tura-Ceide O
- Abstract
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
- Published
- 2023
- Full Text
- View/download PDF
37. Blood Flow Disturbances in Congenital Heart Disease: Is Neuroblastoma Suppressor of Tumorigenicity 1 a Target for Preventing Pulmonary Vascular Remodeling?
- Author
-
Tura-Ceide O
- Subjects
- Humans, Vascular Remodeling, Familial Primary Pulmonary Hypertension, Pulmonary Arterial Hypertension, Heart Defects, Congenital genetics, Heart Defects, Congenital physiopathology, Hypertension, Pulmonary physiopathology, Neuroblastoma
- Published
- 2022
- Full Text
- View/download PDF
38. Differences and Similarities between the Lung Transcriptomic Profiles of COVID-19, COPD, and IPF Patients: A Meta-Analysis Study of Pathophysiological Signaling Pathways.
- Author
-
Aguilar D, Bosacoma A, Blanco I, Tura-Ceide O, Serrano-Mollar A, Barberà JA, and Peinado VI
- Abstract
Coronavirus disease 2019 (COVID-19) is a pandemic respiratory disease associated with high morbidity and mortality. Although many patients recover, long-term sequelae after infection have become increasingly recognized and concerning. Among other sequelae, the available data indicate that many patients who recover from COVID-19 could develop fibrotic abnormalities over time. To understand the basic pathophysiology underlying the development of long-term pulmonary fibrosis in COVID-19, as well as the higher mortality rates in patients with pre-existing lung diseases, we compared the transcriptomic fingerprints among patients with COVID-19, idiopathic pulmonary fibrosis (IPF), and chronic obstructive pulmonary disease (COPD) using interactomic analysis. Patients who died of COVID-19 shared some of the molecular biological processes triggered in patients with IPF, such as those related to immune response, airway remodeling, and wound healing, which could explain the radiological images seen in some patients after discharge. However, other aspects of this transcriptomic profile did not resemble the profile associated with irreversible fibrotic processes in IPF. Our mathematical approach instead showed that the molecular processes that were altered in COVID-19 patients more closely resembled those observed in COPD. These data indicate that patients with COPD, who have overcome COVID-19, might experience a faster decline in lung function that will undoubtedly affect global health.
- Published
- 2022
- Full Text
- View/download PDF
39. Post-COVID-19 patients show an increased endothelial progenitor cell production.
- Author
-
Poyatos P, Luque N, Eizaguirre S, Sabater G, Sebastián L, Francisco-Albesa Í, Peracaula M, Boixadé M, Orriols R, and Tura-Ceide O
- Subjects
- Humans, Male, SARS-CoV-2, COVID-19, Endothelial Progenitor Cells
- Abstract
SARS-CoV-2, the cause of COVID-19, has generated a global emergency. The endothelium is a target of SARS-CoV-2, generating endothelial dysfunction, an essential step for the development of cardiovascular complications. The number of endothelial progenitor cells acts as an indicator of vascular damage. However, its role in SARS-CoV-2 is unknown. The aim of this study was to quantify the number of endothelial colony forming cells (ECFCs) and assess for the first time if there is a significant increase after SARS-CoV-2 infection. This study also evaluates whether the number of ECFC is related to the presence of pulmonary embolism (PE), and if this increase correlates with any of the clinical parameters studied. A total of 63 subjects were recruited including 32 subjects 3-months after overcoming COVID-19 and 31 healthy controls. The results confirm the presence of vascular sequelae in post-COVID-19 patients, with an abnormal increase in the number of ECFCs in blood circulation compared to controls (2.81 ± 2.33 vs 1.23 ± 1.86, P = 0.001). There was no difference in ECFC production in COVID-19 who presented acute PE compared to those that did not (3.21 ± 2.49 vs 2.50 ± 2.23, P > 0.05). The appearance of ECFC colonies in COVID-19 patients was significantly related to male gender (P = 0.003), the presence of systemic hypertension (P = 0.01) and elevated hemoglobin levels (P = 0.02) at the time of ECFC isolation and lower PaO
2 levels (P = 0.01) at admission. Whether these results indicate a prompt response of the patient to repair the damaged endothelium or reflect a postinfection injury that will persist in time is not known., (Copyright © 2022 Elsevier Inc. All rights reserved.)- Published
- 2022
- Full Text
- View/download PDF
40. Endothelial Dysfunction and Cardiovascular Risk in Obstructive Sleep Apnea: A Review Article.
- Author
-
Peracaula M, Torres D, Poyatos P, Luque N, Rojas E, Obrador A, Orriols R, and Tura-Ceide O
- Abstract
Obstructive sleep apnea (OSA) is a respiratory condition during sleep caused by repeated pauses in breathing due to upper airway obstruction. It is estimated that OSA affects 30% of the population, but only 10% are well diagnosed due to the absence of a well-defined symptomatology and poor screening tools for early diagnosis. OSA is associated to an endothelial dysfunction inducing several biological responses such as hypoxia, hypercapnia and oxidative stress, among others. OSA also triggers respiratory, nervous, metabolic, humoral and immunity system activations that increase the possibility of suffering a cardiovascular (CV) disease. In this review, we expose different studies that show the relationship between OSA and endothelial dysfunction and its association with CV pathologies like hypertension, and we define the most well-known treatments and their limitations. Additionally, we describe the potential future directions in OSA research, and we report clinical features such as endothelial progenitor cell alterations that could act as biomarkers for the development of new diagnostic tools and target therapies.
- Published
- 2022
- Full Text
- View/download PDF
41. The Interplay between Pathophysiological Pathways in Early-Onset Severe Preeclampsia Unveiled by Metabolomics.
- Author
-
Youssef L, Crovetto F, Simoes RV, Miranda J, Paules C, Blasco M, Palomo M, García-Calderó H, Tura-Ceide O, Dantas AP, Hernandez-Gea V, Herrero P, Canela N, Campistol JM, Garcia-Pagan JC, Diaz-Ricart M, Gratacos E, and Crispi F
- Abstract
Introduction: Preeclampsia is a multi-system disorder unique to pregnancy responsible for a great part of maternal and perinatal morbidity and mortality. The precise pathogenesis of this complex disorder is still unrevealed., Methods: We examined the pathophysiological pathways involved in early-onset preeclampsia, a specific subgroup representing its most severe presentation, using LC-MS/MS metabolomic analysis based on multi-level extraction of lipids and small metabolites from maternal blood samples, collected at the time of diagnosis from 14 preeclamptic and six matched healthy pregnancies. Statistical analysis comprised multivariate and univariate approaches with the application of over representation analysis to identify differential pathways., Results: A clear difference between preeclamptic and control pregnancies was observed in principal component analysis. Supervised multivariate analysis using orthogonal partial least square discriminant analysis provided a robust model with goodness of fit (R
2 X = 0.91, p = 0.002) and predictive ability (Q2 Y = 0.72, p < 0.001). Finally, univariate analysis followed by 5% false discovery rate correction indicated 82 metabolites significantly altered, corresponding to six overrepresented pathways: (1) aminoacyl-tRNA biosynthesis; (2) arginine biosynthesis; (3) alanine, aspartate and glutamate metabolism; (4) D-glutamine and D-glutamate metabolism; (5) arginine and proline metabolism; and (6) histidine metabolism., Conclusion: Metabolomic analysis focusing specifically on the early-onset severe form of preeclampsia reveals the interplay between pathophysiological pathways involved in this form. Future studies are required to explore new therapeutic approaches targeting these altered metabolic pathways in early-onset preeclampsia.- Published
- 2022
- Full Text
- View/download PDF
42. Generation of a Novel In Vitro Model to Study Endothelial Dysfunction from Atherothrombotic Specimens.
- Author
-
Gallogly S, Fujisawa T, Hung JD, Brittan M, Skinner EM, Mitchell AJ, Medine C, Luque N, Zodda E, Cascante M, Hadoke PW, Mills NL, and Tura-Ceide O
- Subjects
- Animals, Human Umbilical Vein Endothelial Cells, Humans, In Vitro Techniques, Mice, Thrombectomy, Coronary Disease pathology, Endothelial Cells pathology, Thrombosis pathology
- Abstract
Purpose: Endothelial dysfunction is central to the pathogenesis of acute coronary syndrome. The study of diseased endothelium is very challenging due to inherent difficulties in isolating endothelial cells from the coronary vascular bed. We sought to isolate and characterise coronary endothelial cells from patients undergoing thrombectomy for myocardial infarction to develop a patient-specific in vitro model of endothelial dysfunction., Methods: In a prospective cohort study, 49 patients underwent percutaneous coronary intervention with thrombus aspiration. Specimens were cultured, and coronary endothelial outgrowth (CEO) cells were isolated. CEO cells, endothelial cells isolated from peripheral blood, explanted coronary arteries, and umbilical veins were phenotyped and assessed functionally in vitro and in vivo., Results: CEO cells were obtained from 27/37 (73%) atherothrombotic specimens and gave rise to cells with cobblestone morphology expressing CD146 (94 ± 6%), CD31 (87 ± 14%), and von Willebrand factor (100 ± 1%). Proliferation of CEO cells was impaired compared to both coronary artery and umbilical vein endothelial cells (population doubling time, 2.5 ± 1.0 versus 1.6 ± 0.3 and 1.2 ± 0.3 days, respectively). Cell migration was also reduced compared to umbilical vein endothelial cells (29 ± 20% versus 85±19%). Importantly, unlike control endothelial cells, dysfunctional CEO cells did not incorporate into new vessels or promote angiogenesis in vivo., Conclusions: CEO cells can be reliably isolated and cultured from thrombectomy specimens in patients with acute coronary syndrome. Compared to controls, patient-derived coronary endothelial cells had impaired capacity to proliferate, migrate, and contribute to angiogenesis. CEO cells could be used to identify novel therapeutic targets to enhance endothelial function and prevent acute coronary syndromes., (© 2021. The Author(s).)
- Published
- 2021
- Full Text
- View/download PDF
43. Linking In Vitro Models of Endothelial Dysfunction with Cell Senescence.
- Author
-
Jimenez Trinidad FR, Arrieta Ruiz M, Solanes Batlló N, Vea Badenes À, Bobi Gibert J, Valera Cañellas A, Roqué Moreno M, Freixa Rofastes X, Sabaté Tenas M, Dantas AP, Tura-Ceide O, and Rigol Muxart M
- Abstract
Endothelial cell dysfunction is the principal cause of several cardiovascular diseases that are increasing in prevalence, healthcare costs, and mortality. Developing a standardized, representative in vitro model of endothelial cell dysfunction is fundamental to a greater understanding of the pathophysiology, and to aiding the development of novel pharmacological therapies. We subjected human umbilical vein endothelial cells (HUVECs) to different periods of nutrient deprivation or increasing doses of H
2 O2 to represent starvation or elevated oxidative stress, respectively, to investigate changes in cellular function. Both in vitro cellular models of endothelial cell dysfunction-associated senescence developed in this study, starvation and oxidative stress, were validated by markers of cellular senescence (increase in β-galactosidase activity, and changes in senescence gene markers SIRT1 and P21) and endothelial dysfunction as denoted by reductions in angiogenic and migratory capabilities. HUVECs showed a significant H2 O2 concentration-dependent reduction in cell viability ( p < 0.0001), and a significant increase in oxidative stress ( p < 0.0001). Furthermore, HUVECs subjected to 96 h of starvation, or exposed to concentrations of H2 O2 of 400 to 1000 μM resulted in impaired angiogenic and migratory potentials. These models will enable improved physiological studies of endothelial cell dysfunction, and the rapid testing of cellular efficacy and toxicity of future novel therapeutic compounds.- Published
- 2021
- Full Text
- View/download PDF
44. Derivation and characterisation of endothelial cells from patients with chronic thromboembolic pulmonary hypertension.
- Author
-
Tura-Ceide O, Smolders VFED, Aventin N, Morén C, Guitart-Mampel M, Blanco I, Piccari L, Osorio J, Rodríguez C, Rigol M, Solanes N, Malandrino A, Kurakula K, Goumans MJ, Quax PHA, Peinado VI, Castellà M, and Barberà JA
- Subjects
- Apoptosis, Case-Control Studies, Chronic Disease, Endothelium, Vascular pathology, Endothelium, Vascular physiopathology, Female, Humans, Hypertension, Pulmonary physiopathology, Male, Middle Aged, Mitochondria pathology, Oxidative Stress, Pulmonary Artery cytology, Pulmonary Artery pathology, Pulmonary Artery physiopathology, Pulmonary Embolism physiopathology, Endothelium, Vascular cytology, Hypertension, Pulmonary pathology, Pulmonary Embolism pathology
- 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., (© 2021. The Author(s).)
- Published
- 2021
- Full Text
- View/download PDF
45. Circulating Cell Biomarkers in Pulmonary Arterial Hypertension: Relationship with Clinical Heterogeneity and Therapeutic Response.
- Author
-
Tura-Ceide O, Blanco I, Garcia-Lucio J, Del Pozo R, García AR, Ferrer E, Crespo I, Rodríguez-Chiaradia DA, Simeon-Aznar CP, López-Meseguer M, Martín-Ontiyuelo C, Peinado VI, and Barberà JA
- Subjects
- Case-Control Studies, Cell-Derived Microparticles metabolism, Endothelial Cells metabolism, Female, Hemodynamics, Humans, Male, Middle Aged, Pulmonary Arterial Hypertension pathology, Pulmonary Arterial Hypertension physiopathology, Stem Cells metabolism, Treatment Outcome, Biomarkers metabolism, Pulmonary Arterial Hypertension drug therapy, Pulmonary Arterial Hypertension metabolism
- Abstract
Background: Endothelial dysfunction is central to PAH. In this study, we simultaneously analysed circulating levels of endothelial microvesicles (EMVs) and progenitor cells (PCs) in PAH and in controls, as biomarkers of pulmonary endothelial integrity and evaluated differences among PAH subtypes and as a response to treatment., Methods: Forty-seven controls and 144 patients with PAH (52 idiopathic, 9 heritable, 31 associated with systemic sclerosis, 15 associated with other connective tissue diseases, 20 associated with HIV and 17 associated with portal hypertension) were evaluated. Forty-four patients with scleroderma and 22 with HIV infection, but without PAH, were also studied. Circulating levels of EMVs, total (CD31
+ CD42b- ) and activated (CD31+ CD42b- CD62E+ ), as well as circulating PCs (CD34+ CD133+ CD45low ) were measured by flow cytometry and the EMVs/PCs ratio was computed. In treatment-naïve patients, measurements were repeated after 3 months of PAH therapy., Results: Patients with PAH showed higher numbers of EMVs and a lower percentage of PCs, compared with healthy controls. The EMV/PC ratio was increased in PAH patients, and in patients with SSc or HIV without PAH. After starting PAH therapy, individual changes in EMVs and PCs were variable, without significant differences being observed as a group. Conclusion: PAH patients present disturbed vascular homeostasis, reflected in changes in circulating EMV and PC levels, which are not restored with PAH targeted therapy. Combined measurement of circulating EMVs and PCs could be foreseen as a potential biomarker of endothelial dysfunction in PAH.- Published
- 2021
- Full Text
- View/download PDF
46. Reply to: COVID-19 and Coagulopathy.
- Author
-
Rodríguez C, Luque N, Blanco I, Sebastian L, Barberà JA, Peinado VI, and Tura-Ceide O
- Subjects
- Blood Coagulation, Humans, SARS-CoV-2, Blood Coagulation Disorders, COVID-19
- Published
- 2021
- Full Text
- View/download PDF
47. Pulmonary Endothelial Dysfunction and Thrombotic Complications in Patients with COVID-19.
- Author
-
Rodríguez C, Luque N, Blanco I, Sebastian L, Barberà JA, Peinado VI, and Tura-Ceide O
- Subjects
- Angiotensin-Converting Enzyme 2 metabolism, Biomarkers metabolism, COVID-19 pathology, COVID-19 therapy, Endothelium pathology, Endothelium virology, Humans, Membrane Fusion, Pulmonary Embolism pathology, Pulmonary Embolism therapy, Pulmonary Embolism virology, Spike Glycoprotein, Coronavirus metabolism, Thrombosis pathology, Thrombosis therapy, Thrombosis virology, COVID-19 metabolism, Endothelium metabolism, Pulmonary Embolism metabolism, SARS-CoV-2 metabolism, Thrombosis metabolism
- Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a new strain of a Coronaviridae virus that presents 79% genetic similarity to the severe acute respiratory syndrome coronavirus, has been recently recognized as the cause of a global pandemic by the World Health Organization, implying a major threat to world public health. SARS-CoV-2 infects host human cells by binding through the viral spike proteins to the ACE-2 (angiotensin-converting enzyme 2) receptor, fuses with the cell membrane, enters, and starts its replication process to multiply its viral load. Coronavirus disease (COVID-19) was initially considered a respiratory infection that could cause pneumonia. However, in severe cases, it extends beyond the respiratory system and becomes a multiorgan disease. This transition from localized respiratory infection to multiorgan disease is due to two main complications of COVID-19. On the one hand, it is due to the so-called cytokine storm: an uncontrolled inflammatory reaction of the immune system in which defensive molecules become aggressive for the body itself. On the other hand, it is due to the formation of a large number of thrombi that can cause myocardial infarction, stroke, and pulmonary embolism. The pulmonary endothelium actively participates in these two processes, becoming the last barrier before the virus spreads throughout the body. In this review, we examine the role of the pulmonary endothelium in response to COVID-19, the existence of potential biomarkers, and the development of novel therapies to restore vascular homeostasis and to protect and/or treat coagulation, thrombosis patients. In addition, we review the thrombotic complications recently observed in patients with COVID-19 and its potential threatening sequelae.
- Published
- 2021
- Full Text
- View/download PDF
48. The Inflammatory Profile of CTEPH-Derived Endothelial Cells Is a Possible Driver of Disease Progression.
- Author
-
Smolders VFED, Lodder K, Rodríguez C, Tura-Ceide O, Barberà JA, Jukema JW, Quax PHA, Goumans MJ, and Kurakula K
- Subjects
- Endarterectomy, Female, Fluorescence, Gene Expression Regulation, Hemodynamics, Humans, Hypertension, Pulmonary genetics, Hypertension, Pulmonary physiopathology, Inflammation genetics, Inflammation physiopathology, Male, Middle Aged, Phosphorylation, Thromboembolism genetics, Thromboembolism physiopathology, Transcription Factor RelA antagonists & inhibitors, Transcription Factor RelA metabolism, Disease Progression, Endothelial Cells pathology, Hypertension, Pulmonary complications, Hypertension, Pulmonary pathology, Inflammation pathology, Thromboembolism complications, Thromboembolism pathology
- Abstract
Chronic thromboembolic pulmonary hypertension (CTEPH) is a form of pulmonary hypertension characterized by the presence of fibrotic intraluminal thrombi and causing obliteration of the pulmonary arteries. Although both endothelial cell (EC) dysfunction and inflammation are linked to CTEPH pathogenesis, regulation of the basal inflammatory response of ECs in CTEPH is not fully understood. Therefore, in the present study, we investigated the role of the nuclear factor (NF)-κB pro-inflammatory signaling pathway in ECs in CTEPH under basal conditions. Basal mRNA levels of interleukin (IL)-8, IL-1β, monocyte chemoattractant protein-1 (MCP-1), C-C motif chemokine ligand 5 (CCL5), and vascular cell adhesion molecule-1 (VCAM-1) were upregulated in CTEPH-ECs compared to the control cells. To assess the involvement of NF-κB signaling in basal inflammatory activation, CTEPH-ECs were incubated with the NF-κB inhibitor Bay 11-7085. The increase in pro-inflammatory cytokines was abolished when cells were incubated with the NF-κB inhibitor. To determine if NF-κB was indeed activated, we stained pulmonary endarterectomy (PEA) specimens from CTEPH patients and ECs isolated from PEA specimens for phospho-NF-κB-P65 and found that especially the vessels within the thrombus and CTEPH-ECs are positive for phospho-NF-κB-P65. In summary, we show that CTEPH-ECs have a pro-inflammatory status under basal conditions, and blocking NF-κB signaling reduces the production of inflammatory factors in CTEPH-ECs. Therefore, our results show that the increased basal pro-inflammatory status of CTEPH-ECs is, at least partially, regulated through activation of NF-κB signaling and potentially contributes to the pathophysiology and progression of CTEPH.
- Published
- 2021
- Full Text
- View/download PDF
49. Protein network analyses of pulmonary endothelial cells in chronic thromboembolic pulmonary hypertension.
- Author
-
Nukala SB, Tura-Ceide O, Aldini G, Smolders VFED, Blanco I, Peinado VI, Castellà M, Barberà JA, Altomare A, Baron G, Carini M, Cascante M, and D'Amato A
- Subjects
- Endothelial Cells pathology, Humans, Hypertension, Pulmonary pathology, Pulmonary Artery pathology, Pulmonary Embolism pathology, Thromboembolism pathology, Endothelial Cells metabolism, Hypertension, Pulmonary metabolism, Protein Carbonylation, Protein Interaction Maps, Pulmonary Artery metabolism, Pulmonary Embolism metabolism, Thromboembolism metabolism
- 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.
- Published
- 2021
- Full Text
- View/download PDF
50. Complement and coagulation cascades activation is the main pathophysiological pathway in early-onset severe preeclampsia revealed by maternal proteomics.
- Author
-
Youssef L, Miranda J, Blasco M, Paules C, Crovetto F, Palomo M, Torramade-Moix S, García-Calderó H, Tura-Ceide O, Dantas AP, Hernandez-Gea V, Herrero P, Canela N, Campistol JM, Garcia-Pagan JC, Diaz-Ricart M, Gratacos E, and Crispi F
- Subjects
- Adult, Biomarkers blood, Chromatography, Liquid, Complement System Proteins metabolism, Endothelial Cells metabolism, Endothelial Cells pathology, Female, Gestational Age, Humans, Pre-Eclampsia pathology, Pregnancy, Tandem Mass Spectrometry, Blood Coagulation genetics, Complement System Proteins genetics, Pre-Eclampsia blood, Proteomics
- Abstract
Preeclampsia is a pregnancy-specific multisystem disorder and a leading cause of maternal and perinatal morbidity and mortality. The exact pathogenesis of this multifactorial disease remains poorly defined. We applied proteomics analysis on maternal blood samples collected from 14 singleton pregnancies with early-onset severe preeclampsia and 6 uncomplicated pregnancies to investigate the pathophysiological pathways involved in this specific subgroup of preeclampsia. Maternal blood was drawn at diagnosis for cases and at matched gestational age for controls. LC-MS/MS proteomics analysis was conducted, and data were analyzed by multivariate and univariate statistical approaches with the identification of differential pathways by exploring the global human protein-protein interaction network. The unsupervised multivariate analysis (the principal component analysis) showed a clear difference between preeclamptic and uncomplicated pregnancies. The supervised multivariate analysis using orthogonal partial least square discriminant analysis resulted in a model with goodness of fit (R
2 X = 0.99, p < 0.001) and a strong predictive ability (Q2 Y = 0.8, p < 0.001). By univariate analysis, we found 17 proteins statistically different after 5% FDR correction (q-value < 0.05). Pathway enrichment analysis revealed 5 significantly enriched pathways whereby the activation of the complement and coagulation cascades was on top (p = 3.17e-07). To validate these results, we assessed the deposits of C5b-9 complement complex and on endothelial cells that were exposed to activated plasma from an independent set of 4 cases of early-onset severe preeclampsia and 4 uncomplicated pregnancies. C5b-9 and Von Willbrand factor deposits were significantly higher in early-onset severe preeclampsia. Future studies are warranted to investigate potential therapeutic targets for early-onset severe preeclampsia within the complement and coagulation pathway.- Published
- 2021
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.