388 results on '"Joan Albert Barberà"'
Search Results
2. Right Heart Remodeling in Pulmonary Hypertension Associated with Left Heart Disease and Chronic Thromboembolic Pulmonary Hypertension: Insights FBom Cardiac Magnetic Resonance
- Author
-
Blanca Domenech-Ximenos, MD, PhD, Bernardo Ayala, MD, Juan J Rodriguez-Arias, MD, Andrea Arenas, MD, Carmen Palacios, MD, Eduard Solé, MD, Susanna Prat-González, MD, PhD, Alessandro Affronti, MD, PhD, Ivan Vollmer, MD, Marcelo Sánchez, MD, Elena Sandoval, MD, PhD, Daniel Pereda, MD, PhD, Joan Albert Barberà, MD, PhD, Bárbara Vidal, MD, PhD, Isabel Blanco, MD, PhD, Manuel Castella, MD, PhD, and Ana García-Alvarez, MD, PhD
- Subjects
Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Published
- 2024
- Full Text
- View/download PDF
3. Survivin inhibition with YM155 ameliorates experimental pulmonary arterial hypertension
- Author
-
Isabel Blanco, Maribel Marquina, Olga Tura-Ceide, Elisabet Ferrer, Ana M. Ramírez, Manuel Lopez-Meseguer, Maria Callejo, Francisco Perez-Vizcaino, Victor Ivo Peinado, and Joan Albert Barberà
- Subjects
pulmonary circulation ,animal model ,hypoxia ,SU5416 ,YM155 ,pathway ,Therapeutics. Pharmacology ,RM1-950 - 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.
- Published
- 2023
- Full Text
- View/download PDF
4. Elevated plasma levels of epithelial and endothelial cell markers in COVID-19 survivors with reduced lung diffusing capacity six months after hospital discharge
- Author
-
Oriol Sibila, Lídia Perea, Núria Albacar, Jorge Moisés, Tamara Cruz, Núria Mendoza, Belen Solarat, Gemma Lledó, Gerard Espinosa, Joan Albert Barberà, Joan Ramon Badia, Alvar Agustí, Jacobo Sellarés, and Rosa Faner
- Subjects
Post-COVID ,Sequelae ,DLCO ,Epithelial markers ,Endothelial markers ,Diseases of the respiratory system ,RC705-779 - Abstract
Abstract Background Some COVID-19 survivors present lung function abnormalities during follow-up, particularly reduced carbon monoxide lung diffusing capacity (DLCO). To investigate risk factors and underlying pathophysiology, we compared the clinical characteristics and levels of circulating pulmonary epithelial and endothelial markers in COVID-19 survivors with normal or reduced DLCO 6 months after discharge. Methods Prospective, observational study. Clinical characteristics during hospitalization, and spirometry, DLCO and plasma levels of epithelial (surfactant protein (SP) A (SP-A), SP-D, Club cell secretory protein-16 (CC16) and secretory leukocyte protease inhibitor (SLPI)), and endothelial (soluble intercellular adhesion molecule 1 (sICAM-1), soluble E-selectin and Angiopoietin-2) 6 months after hospital discharge were determined in 215 COVID-19 survivors. Results DLCO was
- Published
- 2022
- Full Text
- View/download PDF
5. Derivation and characterisation of endothelial cells from patients with chronic thromboembolic pulmonary hypertension
- Author
-
Olga Tura-Ceide, Valérie F. E. D. Smolders, Núria Aventin, Constanza Morén, Mariona Guitart-Mampel, Isabel Blanco, Lucilla Piccari, Jeisson Osorio, Cristina Rodríguez, Montserrat Rigol, Núria Solanes, Andrea Malandrino, Kondababu Kurakula, Marie Jose Goumans, Paul H. A. Quax, Victor I. Peinado, Manuel Castellà, and Joan Albert Barberà
- Subjects
Medicine ,Science - Abstract
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.
- Published
- 2021
- Full Text
- View/download PDF
6. Effects of Exercise Training on Circulating Biomarkers of Endothelial Function in Pulmonary Arterial Hypertension
- Author
-
Diego A. Rodríguez-Chiaradía, Karys Khilzi, Isabel Blanco, Anna Rodó-Pin, Clara Martin-Ontiyuelo, Anna Herranz Blasco, Jessica Garcia-Lucio, Lluis Molina, Ester Marco, Esther Barreiro, Lucilla Piccari, Victor I. Peinado, Agustín R. Garcia, Olga Tura-Ceide, and Joan Albert Barberà
- Subjects
pulmonary hypertension ,exercise training ,endothelial function ,Biology (General) ,QH301-705.5 - 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
7. Protein network analyses of pulmonary endothelial cells in chronic thromboembolic pulmonary hypertension
- Author
-
Sarath Babu Nukala, Olga Tura-Ceide, Giancarlo Aldini, Valérie F. E. D. Smolders, Isabel Blanco, Victor I. Peinado, Manuel Castellà, Joan Albert Barberà, Alessandra Altomare, Giovanna Baron, Marina Carini, Marta Cascante, and Alfonsina D’Amato
- Subjects
Medicine ,Science - Abstract
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
8. Assessment of Exercise Capacity in Post-COVID-19 Patients: How Is the Appropriate Test Chosen?
- Author
-
Rodrigo Torres-Castro, Rodrigo Núñez-Cortés, Santiago Larrateguy, Xavier Alsina-Restoy, Joan Albert Barberà, Elena Gimeno-Santos, Agustin Roberto García, Oriol Sibila, and Isabel Blanco
- Subjects
exercise capacity ,tests ,post-COVID-19 ,Science - Abstract
There is a wide range of sequelae affecting COVID-19 survivors, including impaired physical capacity. These sequelae can affect the quality of life and return to work of the active population. Therefore, one of the pillars of following-up is the evaluation of physical capacity, which can be assessed with field tests (such as the six-minute walk test, the one-minute standing test, the Chester step test, and the shuttle walking test) or laboratory tests (such as the cardiopulmonary exercise test). These tests can be performed in different contexts and have amply demonstrated their usefulness in the assessment of physical capacity both in post-COVID-19 patients and in other chronic respiratory, metabolic, cardiologic, or neurologic diseases. However, when traditional tests cannot be performed, physical function can be a good substitute, especially for assessing the effects of an intervention. For example, the Short Physical Performance Battery assessment and the Timed Up and Go assessment are widely accepted in older adults. Thus, the test should be chosen according to the characteristics of each subject.
- Published
- 2023
- Full Text
- View/download PDF
9. Changes in REVEAL risk score in patients with pulmonary arterial hypertension treated with macitentan in clinical practice: results from the PRACMA study
- Author
-
Pilar Escribano-Subias, Raquel López, Luis Almenar, María Lázaro, Ian Forn, Anna Torrent, Isabel Blanco, Joan Albert Barberà, and on behalf of the PRACMA investigators
- Subjects
Macitentan ,Observational study ,Pulmonary arterial hypertension ,Risk assessment ,Diseases of the respiratory system ,RC705-779 - Abstract
Abstract Background Macitentan is a dual endothelin receptor antagonist indicated for the long-term treatment of pulmonary arterial hypertension (PAH). We evaluated the change over time in REVEAL risk score in incident and prevalent patients receiving macitentan for the first time. Methods Retrospective, observational study including adult patients with idiopathic/heritable PAH or PAH associated with connective tissue disorders or congenital heart disease treated with macitentan for ≥6-month follow-up in Spain. The REVEAL risk score and risk strata were computed at the start of macitentan and after ≥6-month in patients with ≥7 out of 12 valid REVEAL components. Results Overall, 81 patients (57 for the REVEAL score) were analysed, 77.8% women. The mean age was 57.2 years and 50.6% of patients had idiopathic/heritable PAH. Prevalent patients were 59.3 and 40.7% were incident. Main therapies for PAH included macitentan monotherapy (42.0%) and macitentan in combination with phosphodiesterase type 5 inhibitor (44.4%). With a median time of macitentan treatment of 10.5 months, the mean REVEAL score was 8.7 points at baseline and was 7.2 points after ≥6-month follow-up. The mean change (95% CI) in REVEAL risk score was − 1.4 (− 2.0, − 0.9) points (p
- Published
- 2020
- Full Text
- View/download PDF
10. Progenitor cell mobilisation and recruitment in pulmonary arteries in chronic obstructive pulmonary disease
- Author
-
Olga Tura-Ceide, Sandra Pizarro, Jéssica García-Lucio, Josep Ramírez, Laureano Molins, Isabel Blanco, Yolanda Torralba, Marta Sitges, Cristina Bonjoch, Victor I. Peinado, and Joan Albert Barberà
- Subjects
COPD ,Endothelial dysfunction ,Progenitor cells ,Vascular remodeling ,DLco ,Diseases of the respiratory system ,RC705-779 - Abstract
Abstract Background Pulmonary vascular abnormalities are a characteristic feature of chronic obstructive pulmonary disease (COPD). Cigarette smoking is the most important risk factor for COPD. It is believed that its constant exposure triggers endothelial cell damage and vascular remodelling. Under pathological conditions, progenitor cells (PCs) are mobilized from the bone marrow and recruited to sites of vascular injury. The aim of the study was to investigate whether in COPD the number of circulating PCs is related to the presence of bone marrow-derived cells in pulmonary arteries and the association of these phenomena to both systemic and pulmonary endothelial dysfunction. Methods Thirty-nine subjects, 25 with COPD, undergoing pulmonary resection because of a localized carcinoma, were included. The number of circulating PCs was assessed by flow cytometry using a triple combination of antibodies against CD45, CD133 and CD34. Infiltrating CD45+ cells were identified by immunohistochemistry in pulmonary arteries. Endothelial function in systemic and pulmonary arteries was measured by flow-mediated dilation and adenosine diphosphate-induced vasodilation, respectively. Results COPD patients had reduced numbers of circulating PCs (p
- Published
- 2019
- Full Text
- View/download PDF
11. Differences and Similarities between the Lung Transcriptomic Profiles of COVID-19, COPD, and IPF Patients: A Meta-Analysis Study of Pathophysiological Signaling Pathways
- Author
-
Daniel Aguilar, Adelaida Bosacoma, Isabel Blanco, Olga Tura-Ceide, Anna Serrano-Mollar, Joan Albert Barberà, and Victor Ivo Peinado
- Subjects
chronic lung disease ,transcriptome ,interactome ,cluster analysis ,bioinformatic analysis ,molecular pathway ,Science - 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
12. Phenotypic characterisation of early COPD: a prospective case–control study
- Author
-
Borja G. Cosío, Sergi Pascual-Guardia, Alicia Borras-Santos, Germán Peces-Barba, Salud Santos, Laura Vigil, Juan José Soler-Cataluña, Cristina Martínez-González, Ciro Casanova, Pedro J. Marcos, Carlos J. Alvarez, José Luis López-Campos, Joaquim Gea, Judith Garcia-Aymerich, Jesús Molina, Miguel Román, Jorge Moises, Viktoria Szabo, Elizabeth A. Reagan, Raúl San José Estépar, George Washko, Alvar Agustí, Rosa Faner, Full list of field participating investigators in the study:, Borja G. Cosio, Rocío Cordova Diaz, María Magdalena Pan Naranjo, Joan Palmer Sancho, Miguel Román Rodríguez, Rosa Faner Canet, Joan Albert Barberà, Josep Roca Torrent, Yolanda Torralba Garcia, Jorge Moises Lafuente, Anna Maria Pedro Pijoan, Amparo Hervas Docón, Carmen Herranz, Núria Sanchez Ruano, Diego A ChiaradíaRodríguez, Anna Rodó-Pin, Clara Martín-Ontiyuelo, Mireia Admetlló, Concepción Ballano Castro, Laura Gutiérrez Martín, JoséIgnacio Aoiz Linares, Marta Mourelo Cereijo, Germán Peces-Barba Romero, José Fernández Arias, Carolina Gotera Rivera, Manuel Martin Bernal, Guillermo Gallardo Madueño, Andrés Alcázar Peral, Carmelo Palacios Miras, Maria Teresa Pinedo Moraleda, Maria Belén Torres Labandeira, Mercedes Colomo Rodríguez, María Concepción Rodríguez Gallego, Carmen Lobon Agundez, Mónica Nácher Conches, María José Mansilla, Rosario Serrano Martín, Carlos J. Álvarez Martínez, Marta Padilla Bernáldez, Jesús Molina París, Laura Vigil Giménez, Eduard Monsó Molas, Laia Seto Gort, Mañas Montserrat Baré, Anna Maria Fabra Noguera, JoséLuís López Campos, Carmen Calero Acuña, Laura Carrasco Hernández, Salud Santos Perez, Montserrat Navarro, Elisabeth Serra, Ferran Ferrer Keysers, Damaris Batallé, M Dolores Peleato Catalan, Albert Dorca, Javier Burgos, Juan José, Soler-Cataluña Noelia González García, Lourdes Sánchez Sánchez, Cristina Martínez González, Amador Prieto Fernández, Susana Martínez González, Ciro Casanova Macario, Delia Mayato, Pedro J Marcos Rodriguez, Luis Domínguez Juncal, Rosario Timiraos Carrasco, and Rosa Garcia Palenzuela
- Subjects
Medicine - Abstract
The phenotypic characteristics of chronic obstructive pulmonary disease (COPD) in individuals younger than 50 years of age (early COPD) are not well defined. This prospective, multicentre, case–control study sought to describe these characteristics and compare them with those of smokers (≥10 pack-years) of similar age with normal spirometry (controls). We studied 92 cases (post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC)
- Published
- 2020
- Full Text
- View/download PDF
13. Circulating Cell Biomarkers in Pulmonary Arterial Hypertension: Relationship with Clinical Heterogeneity and Therapeutic Response
- Author
-
Olga Tura-Ceide, Isabel Blanco, Jéssica Garcia-Lucio, Roberto del Pozo, Agustín Roberto García, Elisabet Ferrer, Isabel Crespo, Diego A. Rodríguez-Chiaradia, Carmen Pilar Simeon-Aznar, Manuel López-Meseguer, Clara Martín-Ontiyuelo, Víctor I. Peinado, and Joan Albert Barberà
- Subjects
pulmonary arterial hypertension ,endothelial dysfunction ,biomarkers ,progenitor cells ,endothelial extracellular vesicles ,PAH-specific treatment ,Cytology ,QH573-671 - 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
14. Metabolic Alterations in Cardiopulmonary Vascular Dysfunction
- Author
-
Valérie Françoise Smolders, Erika Zodda, Paul H. A. Quax, Marina Carini, Joan Albert Barberà, Timothy M. Thomson, Olga Tura-Ceide, and Marta Cascante
- Subjects
acute myocardial infarction ,pulmonary hypertension ,endothelial dysfunction ,cellular metabolism ,glycolysis ,metabolic targets ,Biology (General) ,QH301-705.5 - Abstract
Cardiovascular diseases (CVD) are the leading cause of death worldwide. CVD comprise a range of diseases affecting the functionality of the heart and blood vessels, including acute myocardial infarction (AMI) and pulmonary hypertension (PH). Despite their different causative mechanisms, both AMI and PH involve narrowed or blocked blood vessels, hypoxia, and tissue infarction. The endothelium plays a pivotal role in the development of CVD. Disruption of the normal homeostasis of endothelia, alterations in the blood vessel structure, and abnormal functionality are essential factors in the onset and progression of both AMI and PH. An emerging theory proposes that pathological blood vessel responses and endothelial dysfunction develop as a result of an abnormal endothelial metabolism. It has been suggested that, in CVD, endothelial cell metabolism switches to higher glycolysis, rather than oxidative phosphorylation, as the main source of ATP, a process designated as the Warburg effect. The evidence of these alterations suggests that understanding endothelial metabolism and mitochondrial function may be central to unveiling fundamental mechanisms underlying cardiovascular pathogenesis and to identifying novel critical metabolic biomarkers and therapeutic targets. Here, we review the role of the endothelium in the regulation of vascular homeostasis and we detail key aspects of endothelial cell metabolism. We also describe recent findings concerning metabolic endothelial cell alterations in acute myocardial infarction and pulmonary hypertension, their relationship with disease pathogenesis and we discuss the future potential of pharmacological modulation of cellular metabolism in the treatment of cardiopulmonary vascular dysfunction. Although targeting endothelial cell metabolism is still in its infancy, it is a promising strategy to restore normal endothelial functions and thus forestall or revert the development of CVD in personalized multi-hit interventions at the metabolic level.
- Published
- 2019
- Full Text
- View/download PDF
15. The Inflammatory Profile of CTEPH-Derived Endothelial Cells Is a Possible Driver of Disease Progression
- Author
-
Valérie F. E. D. Smolders, Kirsten Lodder, Cristina Rodríguez, Olga Tura-Ceide, Joan Albert Barberà, J. Wouter Jukema, Paul H. A. Quax, Marie José Goumans, and Kondababu Kurakula
- Subjects
chronic thromboembolic pulmonary hypertension ,inflammation ,nuclear factor-κB signaling ,endothelial dysfunction ,Cytology ,QH573-671 - 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
16. Imbalance between endothelial damage and repair capacity in chronic obstructive pulmonary disease.
- Author
-
Jéssica García-Lucio, Victor I Peinado, Lluís de Jover, Roberto Del Pozo, Isabel Blanco, Cristina Bonjoch, Núria Coll-Bonfill, Tanja Paul, Olga Tura-Ceide, and Joan Albert Barberà
- Subjects
Medicine ,Science - Abstract
Circulating endothelial microparticles (EMPs) and progenitor cells (PCs) are biological markers of endothelial function and endogenous repair capacity. The study was aimed to investigate whether COPD patients have an imbalance between EMPs to PCs compared to controls and to evaluate the effect of cigarette smoke on these circulating markers.Circulating EMPs and PCs were determined by flow cytometry in 27 nonsmokers, 20 smokers and 61 COPD patients with moderate to severe airflow obstruction. We compared total EMPs (CD31+CD42b-), apoptotic if they co-expressed Annexin-V+ or activated if they co-expressed CD62E+, circulating PCs (CD34+CD133+CD45+) and the EMPs/PCs ratio between groups.COPD patients presented increased levels of total and apoptotic circulating EMPs, and an increased EMPs/PCs ratio, compared with nonsmokers. Women had less circulating PCs than men through all groups and those with COPD showed lower levels of PCs than both control groups. In smokers, circulating EMPs and PCs did not differ from nonsmokers, being the EMPs/PCs ratio in an intermediate position between COPD and nonsmokers.We conclude that COPD patients present an imbalance between endothelial damage and repair capacity that might explain the frequent concurrence of cardiovascular disorders. Factors related to the disease itself and gender, rather than cigarette smoking, may account for this imbalance.
- Published
- 2018
- Full Text
- View/download PDF
17. Persistence of Breakage in Specific Chromosome Bands 6 Years after Acute Exposure to Oil.
- Author
-
Alexandra Francés, Kristin Hildur, Joan Albert Barberà, Gema Rodríguez-Trigo, Jan-Paul Zock, Jesús Giraldo, Gemma Monyarch, Emma Rodriguez-Rodriguez, Fernanda de Castro Reis, Ana Souto, Federico P Gómez, Francisco Pozo-Rodríguez, Cristina Templado, and Carme Fuster
- Subjects
Medicine ,Science - Abstract
BACKGROUND:The identification of breakpoints involved in chromosomal damage could help to detect genes involved in genetic disorders, most notably cancer. Until now, only one published study, carried out by our group, has identified chromosome bands affected by exposure to oil from an oil spill. In that study, which was performed two years after the initial oil exposure in individuals who had participated in clean-up tasks following the wreck of the Prestige, three chromosomal bands (2q21, 3q27, 5q31) were found to be especially prone to breakage. A recent follow-up study, performed on the same individuals, revealed that the genotoxic damage had persisted six years after oil exposure. OBJECTIVES:To determine whether there exist chromosome bands which are especially prone to breakages and to know if there is some correlation with those detected in the previous study. In addition, to investigate if the DNA repair problems detected previously persist in the present study. DESIGN:Follow-up study performed six years after the Prestige oil spill. SETTING:Fishermen cooperatives in coastal villages. PARTICIPANTS:Fishermen highly exposed to oil spill who participated in previous genotoxic study six years after the oil. MEASUREMENTS:Chromosome damage in peripheral lymphocytes. For accurate identification of the breakpoints involved in chromosome damage of circulating lymphocytes, a sequential stain/G-banding technique was employed. To determine the most break-prone chromosome bands, two statistical methods, the Fragile Site Multinomial and the chi-square tests (where the bands were corrected by their length) were used. To compare the chromosome lesions, structural chromosome alterations and gaps/breaks between two groups of individuals we used the GEE test which takes into account a possible within-individual correlation. Dysfunctions in DNA repair mechanisms, expressed as chromosome damage, were assessed in cultures with aphidicolin by the GEE test. RESULTS:Cytogenetic analyses were performed in 47 exposed individuals. A total of 251 breakpoints in exposed individuals) were identified, showing a non-uniform distribution in the human ideogram. Ten chromosome bands were found to be especially prone to breakage through both statistical methods. By comparing these bands with those observed in certain exposed individuals who had already participated the previous study, it was found in both studies that four bands (2q21, 3q27, 5q31 and 17p11.2) are particularly sensitive to breakage. Additionally, the dysfunction in DNA repair mechanisms was not significantly higher in oil-exposed individuals than in non-exposed individuals. LIMITATIONS:The sample size and the possibility of some kind of selection bias should be considered. Genotoxic results cannot be extrapolated to the high number of individuals who participated occasionally in clean-up tasks. CONCLUSION:Our findings show the existence of at least four target bands (2q21, 3q27, 5q31 and 17p11.2) with a greater propensity to break over time after an acute exposure to oil. The breaks in these bands, which are commonly involved in hematological cancer, may explain the increase of cancer risk reported in chronically benzene-exposed individuals. In addition, a more efficiency of the DNA repair mechanisms has been detected six years after in fishermen who were highly exposed to the oil spill. To date, only this study, performed by our group on the previous and present genotoxic effects, has analyzed the chromosomal regions affected by breakage after an acute oil exposure.
- Published
- 2016
- Full Text
- View/download PDF
18. Slug Is Increased in Vascular Remodeling and Induces a Smooth Muscle Cell Proliferative Phenotype.
- Author
-
Núria Coll-Bonfill, Victor I Peinado, María V Pisano, Marcelina Párrizas, Isabel Blanco, Maurits Evers, Julia C Engelmann, Jessica García-Lucio, Olga Tura-Ceide, Gunter Meister, Joan Albert Barberà, and Melina M Musri
- Subjects
Medicine ,Science - Abstract
Previous studies have confirmed Slug as a key player in regulating phenotypic changes in several cell models, however, its role in smooth muscle cells (SMC) has never been assessed. The purpose of this study was to evaluate the expression of Slug during the phenotypic switch of SMC in vitro and throughout the development of vascular remodeling.Slug expression was decreased during both cell-to-cell contact and TGFβ1 induced SMC differentiation. Tumor necrosis factor-α (TNFα), a known inductor of a proliferative/dedifferentiated SMC phenotype, induces the expression of Slug in SMC. Slug knockdown blocked TNFα-induced SMC phenotypic change and significantly reduced both SMC proliferation and migration, while its overexpression blocked the TGFβ1-induced SMC differentiation and induced proliferation and migration. Genome-wide transcriptomic analysis showed that in SMC, Slug knockdown induced changes mainly in genes related to proliferation and migration, indicating that Slug controls these processes in SMC. Notably, Slug expression was significantly up-regulated in lungs of mice using a model of pulmonary hypertension-related vascular remodeling. Highly remodeled human pulmonary arteries also showed an increase of Slug expression compared to less remodeled arteries.Slug emerges as a key transcription factor driving SMC towards a proliferative phenotype. The increased Slug expression observed in vivo in highly remodeled arteries of mice and human suggests a role of Slug in the pathogenesis of pulmonary vascular diseases.
- Published
- 2016
- Full Text
- View/download PDF
19. Correction: Slug Is Increased in Vascular Remodeling and Induces a Smooth Muscle Cell Proliferative Phenotype.
- Author
-
Núria Coll-Bonfill, Victor I Peinado, María V Pisano, Marcelina Párrizas, Isabel Blanco, Maurits Evers, Julia C Engelmann, Jessica García-Lucio, Olga Tura-Ceide, Gunter Meister, Joan Albert Barberà, and Melina M Musri
- Subjects
Medicine ,Science - Abstract
[This corrects the article DOI: 10.1371/journal.pone.0159460.].
- Published
- 2016
- Full Text
- View/download PDF
20. Follow-Up Genotoxic Study: Chromosome Damage Two and Six Years after Exposure to the Prestige Oil Spill.
- Author
-
Kristin Hildur, Cristina Templado, Jan-Paul Zock, Jesús Giraldo, Francisco Pozo-Rodríguez, Alexandra Frances, Gemma Monyarch, Gema Rodríguez-Trigo, Emma Rodriguez-Rodriguez, Ana Souto, Federico P Gómez, Josep M Antó, Joan Albert Barberà, and Carme Fuster
- Subjects
Medicine ,Science - Abstract
The north-west coast of Spain was heavily contaminated by the Prestige oil spill, in 2002. Individuals who participated in the clean-up tasks showed increased chromosome damage two years after exposure. Long-term clinical implications of chromosome damage are still unknown.To realize a follow-up genotoxic study to detect whether the chromosome damage persisted six years after exposure to the oil.Follow-up study.Fishermen cooperatives in coastal villages.Local fishermen who were highly exposed (n = 52) and non-exposed (n = 23) to oil seven years after the spill.Chromosome damage in circulating lymphocytes.Chromosome damage in exposed individuals persists six years after oil exposure, with a similar incidence than those previously detected four years before. A surprising increase in chromosome damage in non-exposed individual was found six years after Prestige spill vs. those detected two years after the exposure.The sample size and the possibility of some kind of selection bias should be considered. Genotoxic results cannot be extrapolated to the approximately 300,000 individuals who participated occasionally in clean-up tasks.The persistence of chromosome damage detected in exposed individuals six years after oil exposure seems to indicate that the cells of the bone marrow are affected. A surprising increase in chromosome damage in non-exposed individuals detected in the follow-up study suggests an indirect exposition of these individuals to some oil compounds or to other toxic agents during the last four years. More long-term studies are needed to confirm the presence of chromosome damage in exposed and non-exposed fishermen due to the association between increased chromosomal damage and increased risk of cancer. Understanding and detecting chromosome damage is important for detecting cancer in its early stages. The present work is the first follow-up cytogenetic study carried out in lymphocytes to determine genotoxic damage evolution between two and six years after oil exposure in same individuals.
- Published
- 2015
- Full Text
- View/download PDF
21. Circulating progenitor cells and vascular dysfunction in chronic obstructive pulmonary disease.
- Author
-
Sandra Pizarro, Jéssica García-Lucio, Víctor I Peinado, Olga Tura-Ceide, Marta Díez, Isabel Blanco, Marta Sitges, Jordi Petriz, Yolanda Torralba, Pedro Marín, Josep Roca, and Joan Albert Barberà
- Subjects
Medicine ,Science - Abstract
In chronic obstructive pulmonary disease (COPD), decreased progenitor cells and impairment of systemic vascular function have been suggested to confer higher cardiovascular risk. The origin of these changes and their relationship with alterations in the pulmonary circulation are unknown.To investigate whether changes in the number of circulating hematopoietic progenitor cells are associated with pulmonary hypertension or changes in endothelial function.62 COPD patients and 35 controls (18 non-smokers and 17 smokers) without cardiovascular risk factors other than cigarette smoking were studied. The number of circulating progenitors was measured as CD45(+)CD34(+)CD133(+) labeled cells by flow cytometry. Endothelial function was assessed by flow-mediated dilation. Markers of inflammation and angiogenesis were also measured in all subjects.Compared with controls, the number of circulating progenitor cells was reduced in COPD patients. Progenitor cells did not differ between control smokers and non-smokers. COPD patients with pulmonary hypertension showed greater number of progenitor cells than those without pulmonary hypertension. Systemic endothelial function was worse in both control smokers and COPD patients. Interleukin-6, fibrinogen, high sensitivity C-reactive protein, vascular endothelial growth factor and tumor necrosis factor were increased in COPD. In COPD patients, the number of circulating progenitor cells was inversely related to the flow-mediated dilation of systemic arteries.Pulmonary and systemic vascular impairment in COPD is associated with cigarette smoking but not with the reduced number of circulating hematopoietic progenitors. The latter appears to be a consequence of the disease itself not related to smoking habit.
- Published
- 2014
- Full Text
- View/download PDF
22. Chromosomal bands affected by acute oil exposure and DNA repair errors.
- Author
-
Gemma Monyarch, Fernanda de Castro Reis, Jan-Paul Zock, Jesús Giraldo, Francisco Pozo-Rodríguez, Ana Espinosa, Gema Rodríguez-Trigo, Hector Verea, Gemma Castaño-Vinyals, Federico P Gómez, Josep M Antó, Maria Dolors Coll, Joan Albert Barberà, and Carme Fuster
- Subjects
Medicine ,Science - Abstract
BackgroundIn a previous study, we showed that individuals who had participated in oil clean-up tasks after the wreckage of the Prestige presented an increase of structural chromosomal alterations two years after the acute exposure had occurred. Other studies have also reported the presence of DNA damage during acute oil exposure, but little is known about the long term persistence of chromosomal alterations, which can be considered as a marker of cancer risk.ObjectivesWe analyzed whether the breakpoints involved in chromosomal damage can help to assess the risk of cancer as well as to investigate their possible association with DNA repair efficiency.MethodsCytogenetic analyses were carried out on the same individuals of our previous study and DNA repair errors were assessed in cultures with aphidicolin.ResultsThree chromosomal bands, 2q21, 3q27 and 5q31, were most affected by acute oil exposure. The dysfunction in DNA repair mechanisms, expressed as chromosomal damage, was significantly higher in exposed-oil participants than in those not exposed (p= 0.016).ConclusionThe present study shows that breaks in 2q21, 3q27 and 5q31 chromosomal bands, which are commonly involved in hematological cancer, could be considered useful genotoxic oil biomarkers. Moreover, breakages in these bands could induce chromosomal instability, which can explain the increased risk of cancer (leukemia and lymphomas) reported in chronically benzene-exposed individuals. In addition, it has been determined that the individuals who participated in clean-up of the oil spill presented an alteration of their DNA repair mechanisms two years after exposure.
- Published
- 2013
- Full Text
- View/download PDF
23. Atrophy signaling pathways in respiratory and limb muscles of guinea pigs exposed to chronic cigarette smoke: role of soluble guanylate cyclase stimulation
- Author
-
Víctor Ivo Peinado, Maria Guitart, Isabel Blanco, Olga Tura-Ceide, Tanja Paul, Joan Albert Barberà, and Esther Barreiro
- Subjects
Pulmonary and Respiratory Medicine ,Physiology ,Physiology (medical) ,Cell Biology - 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
24. Home Oxygen Monitoring in Patients with Interstitial Lung Disease
- Author
-
Carme Hernandez, Nuria Albacar, Joel Francesqui, Jacobo Sellares, Joan Albert Barberà, Isabel Blanco, Sandra Cuerpo Cardeñosa, Xavier Alsina, Fernanda Hernandez-Gonzalez, Cristina Embid, and Maria Palomo
- Subjects
Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,business.industry ,Home oxygen ,Oxygen Inhalation Therapy ,Interstitial lung disease ,medicine.disease ,Home Care Services ,Gastroenterology ,Oxygen ,Internal medicine ,medicine ,Humans ,In patient ,Lung Diseases, Interstitial ,business - Published
- 2022
25. Hipertensión pulmonar tromboembólica crónica en España: una década de cambio
- Author
-
Manuel López-Meseguer, Cristina Fernández Pérez, Antonio Lara-Padrón, Raquel López-Reyes, Isabel Blanco, Paula Martínez-Santos, Amaya Martínez-Meñaca, Pilar Escribano-Subías, María Teresa Velázquez-Martín, Juan Antonio Domingo-Morera, and Joan Albert Barberà
- Subjects
03 medical and health sciences ,0302 clinical medicine ,business.industry ,Medicine ,030204 cardiovascular system & hematology ,Cardiology and Cardiovascular Medicine ,business ,Humanities - Abstract
Resumen Introduccion y objetivos El tratamiento de la hipertension pulmonar tromboembolica cronica (HTPTEC) ha evolucionado en la ultima decada. Sin embargo, apenas se dispone de informacion sobre el impacto de estos logros en la poblacion general a escala nacional. Este estudio se diseno para describir las caracteristicas de los pacientes con HTPTEC en Espana en la ultima decada. Metodos Se recogieron prospectivamente datos epidemiologicos, clinicos y pronosticos de los pacientes con HTPTEC consecutivos incluidos en el registro espanol REHAP desde el 1 de enero de 2007 al 31 de diciembre de 2018. Se evaluaron las diferencias entre diferentes periodos de tiempo, estableciendo 2013 como fecha de referencia para el analisis. Se calculo la puntuacion de propension para la intervencion mediante un modelo multivariable de regresion logistica. Resultados Se incluyo a 1.019 pacientes; se remitio a 659 (64,4%) a un centro nacional de referencia en HTPTEC. Del total, se selecciono a 350 (34,3%) para cirugia y a 97 (9,6%) para tratamiento percutaneo. Entre los pacientes diagnosticados entre 2007 y 2012 hubo mas frecuencia de muerte que entre los diagnosticados de 2013 en adelante (HR = 1,83; IC95%, 1,07-3,15; p = 0,027). En el grupo de pacientes ajustado por el modelo de puntuacion de propension, las resistencias vasculares pulmonares basales y la distancia recorrida en el test de 6 min de marcha tambien fueron determinantes del pronostico (respectivamente, HR = 1,24; IC95%, 1,15-1,33; p = 0,011, y HR = 0,93; IC95%, 0,90-0,97; p = 0,001). Las tasas de supervivencia de los pacientes que se sometieron a un procedimiento intervencionista (trombendarterectomia pulmonar o angioplastia con balon de arterias pulmonares) resultaron llamativamente altas. Conclusiones Durante la ultima decada, el diagnostico y el pronostico de la HTPTEC han mejorado de manera considerable. La gravedad de la enfermedad al diagnostico determino el perfil de riesgo. Los pacientes a los que se realizaron trombendarterectomia pulmonar o angioplastia con balon de arterias pulmonares tuvieron mejores resultados.
- Published
- 2021
26. Effect of a Soluble Guanylate Cyclase Stimulator on the Purinergic Pathway in an Animal Model of Emphysema Induced by Cigarette Smoke
- Author
-
Ester Cuevas, Elisabet Aliagas, Tanja Paul, Yuliana Pascual-González, Marta López-Sánchez, Joan Albert Barberà, Jordi Dorca, Víctor Ivo Peinado, and Salud Santos
- Abstract
Purinergic and nitric oxide (NO) signaling pathways appear to be involved in the development of emphysema and vascular remodeling of chronic obstructive pulmonary disease (COPD). In an animal model, we evaluate the gene and protein expression of ENTPD1/CD39 and NT5E/CD73, and the effect on this expression of a guanylate cyclase (GC) stimulator. Forty-two guinea pigs underwent sham exposure (SHAM) or cigarette smoke (CS) exposure from three to six months. They were divided into six groups (sham-exposed, smokers or former smokers) and treated with vehicle (VH) or BAY 41-2272 (GC stimulator) for three months. Immunohistochemistry, western blot and qPCR assays were performed on lung tissue samples. Compared to SHAM + VH, ENTPD1 and NT5E were downregulated in the CS + VH group (1 ± 0 vs. 0.78 ± 0.51, p > 0.05, and 1 ± 0 vs. 0.45 ± 0.27, p = 0.027 respectively). Treatment with BAY 41-2722 increased ENTPD1 and NT5E expression to 1.06 ± 0.4 and 0.71 ± 0.35, respectively. No changes in the Ex-CS + BAY group were found. NT5E/CD73 was downregulated in the lungs of an animal model of emphysema. Treatment with a soluble GC stimulator tended to restore the gene and protein expression of ENTPD1/CD39 and NT5E/CD73 in smoke-exposed animals, suggesting its implication in a new mechanism for preventing emphysema.
- Published
- 2022
27. Pulmonary Endothelial Dysfunction and Thrombotic Complications in Patients with COVID-19
- Author
-
Neus Luque, Laura Sebastian, Isabel Blanco, Olga Tura-Ceide, Cristina Rodríguez, Victor I. Peinado, and Joan Albert Barberà
- Subjects
0301 basic medicine ,Pulmonary and Respiratory Medicine ,pulmonary embolism ,Clinical Biochemistry ,coagulation/thrombosis ,Disease ,medicine.disease_cause ,Membrane Fusion ,03 medical and health sciences ,0302 clinical medicine ,Correspondence ,medicine ,Humans ,Coronaviridae ,Endothelium ,Endothelial dysfunction ,Molecular Biology ,Coronavirus ,biology ,SARS-CoV-2 ,business.industry ,Respiratory infection ,COVID-19 ,Thrombosis ,Cell Biology ,medicine.disease ,biology.organism_classification ,Pneumonia ,030104 developmental biology ,030228 respiratory system ,Spike Glycoprotein, Coronavirus ,Immunology ,endothelial cell ,Angiotensin-Converting Enzyme 2 ,Cytokine storm ,business ,Viral load ,Biomarkers ,Perspectives - Abstract
SARS-CoV-2, a new strain of a Coronaviridae virus which presents 79% genetic similarity to the severe acute respiratory syndrome coronavirus (SARS-CoV) has been recently recognized as the cause of a global pandemic by the World Health Organization (WHO) implying a major threat to the world public health. SARS-CoV-2 infects host human cells by binding through the viral spike proteins to the angiotensin-converting enzyme 2 (ACE-2) receptor, fuses with the cell membrane, enters and starts its replication process in order 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 multi-organ disease. This transition from localized respiratory infection to multi-organ disease is due to two main complications of COVID-19. On the one hand, 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, the formation of a large number of thrombi that can cause myocardial infarction, stroke and pulmonary embolism (PE). 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/treat these patients. Additionally, we review the thrombotic complications recently observed in COVID-19 patients and its potential threatening sequelae. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).
- Published
- 2021
28. Association Between Systemic and Pulmonary Vascular Dysfunction in COPD
- Author
-
Lucilla Piccari, Joan Albert Barberà, Jorge Moisés, Isabel Blanco, Victor I. Peinado, Roberto Del Pozo, Jéssica García-Lucio, Olga Tura-Ceide, Marta Sitges, and Yolanda Torralba
- Subjects
medicine.medical_specialty ,COPD ,Vascular disease ,business.industry ,General Medicine ,medicine.disease ,respiratory tract diseases ,03 medical and health sciences ,0302 clinical medicine ,030228 respiratory system ,DLCO ,Diffusing capacity ,Internal medicine ,medicine.artery ,Pulmonary artery ,cardiovascular system ,medicine ,Cardiology ,Arterial stiffness ,030212 general & internal medicine ,Endothelial dysfunction ,business ,Pulse wave velocity - Abstract
Introduction 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.
- Published
- 2020
29. Updated Perspectives on Pulmonary Hypertension in COPD
- Author
-
Isabel Blanco, Victor I. Peinado, Olga Tura-Ceide, and Joan Albert Barberà
- Subjects
medicine.medical_specialty ,COPD ,Exacerbation ,business.industry ,Vascular disease ,Respiratory impairment ,General Medicine ,medicine.disease ,Pulmonary hypertension ,03 medical and health sciences ,Therapeutic approach ,0302 clinical medicine ,030228 respiratory system ,medicine.artery ,Internal medicine ,Pulmonary artery ,medicine ,Cardiology ,030212 general & internal medicine ,Complication ,business - Abstract
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.
- Published
- 2020
30. Pulmonary chronic thromboembolic disease
- Author
-
Remedios Otero, Purificación Ramírez, and Joan Albert Barberà
- Subjects
medicine.medical_specialty ,business.industry ,General Medicine ,medicine.disease ,Pulmonary hypertension ,Asymptomatic ,Pulmonary embolism ,03 medical and health sciences ,Therapeutic approach ,0302 clinical medicine ,030228 respiratory system ,Embolism ,Internal medicine ,medicine ,Cardiology ,Thromboembolic disease ,Chronic thromboembolic pulmonary hypertension ,In patient ,medicine.symptom ,business - Abstract
Persistent thrombotic lesions are common in patients with pulmonary embolism. These lesions occur on a clinical spectrum, ranging from an asymptomatic course with complete functional recovery to chronic thromboembolic pulmonary hypertension. The concept of chronic thromboembolic disease has emerged in recent years to describe a subgroup of patients with persistent thrombotic lesions who have symptoms on exertion and pulmonary vascular dysfunction, but no pulmonary hypertension at rest. The prevalence of this entity is unknown and the criteria for diagnosing it are not defined. The aim of this article is to analyze post-pulmonary embolism sequelae and review existing evidence on chronic thromboembolic disease, with special emphasis on its diagnosis and therapeutic approach.
- Published
- 2020
31. Does arterial oxygenation during exercise add prognostic value in pulmonary arterial hypertension?
- Author
-
Xavier Alsina-Restoy, Rodrigo Torres-Castro, Yolanda Torralba-García, Felip Burgos, Joan Albert Barberà, Àlvar Agustí, and Isabel Blanco
- Subjects
Pulmonary and Respiratory Medicine - Abstract
The 6-min walking distance (6MWD) is often used to assess prognosis in pulmonary arterial hypertension (PAH) patients. Whether or not changes in arterial oxygen saturation (SpOAmbispective study that includes 137 patients with PAH: 38 idiopathic/heritable (i/h PAH), 42 with connective tissue disease (CTD-PAH), 34 with porto-pulmonary hypertension (PoPH), 21 with HIV-associated PAH and 2 with pulmonary venous occlusive disease (PVOD). Patients were characterized and, treated according to international recommendations, and were followed-up for 5 years. To integrate SpO(1) during follow-up, 40 patients died (29.2%); (2) results confirmed the prognostic value of the 6MWD (AUC 0.913 [IQR 0.868-0.958]; p 0.0001), original DDR (AUC 0.923 [0.881-0.966]; p 0.001), New DDR (AUC 0.917 [0.872-0.961], p 0.001), and DSP (AUC 0.914 [0.869-0.959], p 0.001); and, (3) neither the original or new DDR or DSP added significant prognostic value to 6MWD in these patients.Consideration of three different composite indices of arterial oxygenation changes during exercise does not add prognostic value to that of the 6MWD in patients with PAH.
- Published
- 2023
32. Tolerancia al esfuerzo en la hipertensión pulmonar
- Author
-
Isabel Blanco, Rodrigo Torres-Castro, and Joan Albert Barberà
- Subjects
Pulmonary and Respiratory Medicine - Published
- 2022
33. [Translated article] Exercise Tolerance in Pulmonary Hypertension
- Author
-
Isabel Blanco, Rodrigo Torres-Castro, and Joan Albert Barberà
- Subjects
Pulmonary and Respiratory Medicine - Published
- 2022
34. Reply to: COVID-19 and Coagulopathy
- Author
-
Cristina Rodríguez, Victor I. Peinado, Laura Sebastian, Isabel Blanco, Olga Tura-Ceide, Neus Luque, and Joan Albert Barberà
- Subjects
Pulmonary and Respiratory Medicine ,2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,business.industry ,SARS-CoV-2 ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Clinical Biochemistry ,COVID-19 ,Thrombosis ,Cell Biology ,Blood Coagulation Disorders ,medicine.disease ,Virology ,Correspondence ,Coagulopathy ,Medicine ,Humans ,business ,Molecular Biology ,Lung - Published
- 2021
35. Long-Term Respiratory and Genotoxic Effects in The Prestige Oil Spill
- Author
-
Joan Albert Barberà, Gema Rodríguez-Trigo, and Jan-Paul Zock
- Subjects
Prestige ,Environmental health ,Oil spill ,General Engineering ,General Earth and Planetary Sciences ,Environmental science ,General Environmental Science ,Term (time) - Published
- 2021
36. Derivation and characterisation of endothelial cells from patients with chronic thromboembolic pulmonary hypertension
- Author
-
Paul H.A. Quax, Montserrat Rigol, Mariona Guitart-Mampel, Núria Aventín, Valérie F E D Smolders, Jeisson Osorio, Victor I. Peinado, Lucilla Piccari, Kondababu Kurakula, Isabel Blanco, Cristina Rodríguez, Olga Tura-Ceide, Constanza Morén, Manuel Castellá, Andrea Malandrino, Núria Solanes, Joan Albert Barberà, Marie-José Goumans, Universitat Politècnica de Catalunya. Departament de Ciència i Enginyeria de Materials, Universitat Politècnica de Catalunya. BBT - Grup de recerca en Biomaterials, Biomecànica i Enginyeria de Teixits, Hospital Clínic i Provincial de Barcelona, Institut de Bioenginyeria de Catalunya, Universiteit Leiden, Pulmonary medicine, Physiology, and ACS - Pulmonary hypertension & thrombosis
- Subjects
Male ,Science ,Hypertension, Pulmonary ,Apoptosis ,Bioengineering ,Pulmonary Artery ,medicine.disease_cause ,Endoteli ,Pulmonary hypertension ,In vivo ,Enos ,medicine ,Humans ,Bioenginyeria ,Endothelium ,Endothelial dysfunction ,chemistry.chemical_classification ,Embòlia pulmonar ,Hipertensió pulmonar ,Reactive oxygen species ,Multidisciplinary ,biology ,Cell adhesion molecule ,Enginyeria biomèdica [Àrees temàtiques de la UPC] ,Pulmonary embolism ,Middle Aged ,medicine.disease ,biology.organism_classification ,Mitochondria ,Endothelial stem cell ,Oxidative Stress ,chemistry ,Case-Control Studies ,Chronic Disease ,Cancer research ,Medicine ,Female ,Endothelium, Vascular ,Pulmonary Embolism ,Oxidative stress - Abstract
Rationale: 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. Methods: 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. Results: 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. Conclusions: 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.
- Published
- 2021
37. Gas exchange impairment in COPD with severe pulmonary hypertension
- Author
-
Joan Albert Barberà, Lucilla Piccari, Isabel Blanco, Ana Ramírez, Jorge Moisés, Felip Burgos, Yolanda Torralba, Concepción Gistau, and Ebymar Arismendi
- Subjects
medicine.medical_specialty ,COPD ,business.industry ,Internal medicine ,Gas exchange impairment ,medicine ,Cardiology ,medicine.disease ,business ,Pulmonary hypertension - Published
- 2021
38. 18-FDG uptake on PET-CT and metabolism in pulmonary arterial hypertension
- Author
-
Daniel Aguilar, Aida Ninerola, Jeisson Osorio Trujillo, Pilar Paredes, Manel Castella, Yolanda Torralba, Joan Albert Barberà, Valérie F E D Smolders, Jesús Ruiz-Cabello, Javier Pavía, Victor I. Peinado, Isabel Blanco, Laura Sebastian, Ivan Vollmer, Lucilla Piccari, and Olga Tura-Ceide
- Subjects
PET-CT ,business.industry ,Fdg uptake ,Medicine ,Metabolism ,business ,Nuclear medicine - Published
- 2021
39. Soluble guanylate cyclase stimulators revert in vitro cigarette smoke effects through JNK pathway normalization
- Author
-
Adelaida Bosacoma, Victor I. Peinado, Tanja Paul, Daniel Aguilar, Isabel Blanco, Joan Albert Barberà, and Olga Tura-Ceide
- Subjects
Normalization (statistics) ,business.industry ,Guanylate Cyclase Stimulators ,JNK Pathway ,Cigarette smoke ,Medicine ,Pharmacology ,business ,In vitro - Published
- 2021
40. Selection of a gene panel related to pulmonary hypertension associated with respiratory diseases
- Author
-
Daniel Aguilar, Adelaida Bosacoma, Joan Albert Barberà, Isabel Blanco, Clara Martín-Ontiyuelo, Victor I. Peinado, Ana Ramírez, Olga Tura-Ceide, Ylenia Roger, Jeisson Osorio, and Agustin Roberto Garcia
- Subjects
business.industry ,medicine ,Respiratory system ,medicine.disease ,Bioinformatics ,business ,Pulmonary hypertension ,Gene ,Selection (genetic algorithm) - Published
- 2021
41. Differential expression of plasma microRNAs in chronic thromboembolic pulmonary hypertension and pulmonary embolism related to occult cancer
- Author
-
Verónica Sánchez-López, Victor I. Peinado, Carme Font, David Hervás, Joan Albert Barberà, Julia Oto, Pilar Medina, Cristina Bonjoch, Isabel Blanco, Elena Arellano, Remedios Otero, Jeisson Osorio, and Olga Tura-Ceide
- Subjects
medicine.medical_specialty ,business.industry ,Internal medicine ,microRNA ,medicine ,Cardiology ,Chronic thromboembolic pulmonary hypertension ,Occult cancer ,Differential expression ,business ,medicine.disease ,Pulmonary embolism - Published
- 2021
42. Novel hypoxia system to assess endothelial dysfunction in chronic thromboembolic pulmonary hypertension (CTEPH)
- Author
-
Esther Marhuenda, Isaac Almendros, Victor I. Peinado, Manuel Castellá, Ylenia Roger, Joan Albert Barberà, Ana Ramírez, Isabel Blanco, and Olga Tura-Ceide
- Subjects
medicine.medical_specialty ,business.industry ,Internal medicine ,medicine ,Cardiology ,Chronic thromboembolic pulmonary hypertension ,Endothelial dysfunction ,Hypoxia (medical) ,medicine.symptom ,medicine.disease ,business - Published
- 2021
43. Predictors of response to phosphodiesterase-5 inhibitors in pulmonary arterial hypertension
- Author
-
Olga Tura, Juan Antonio Domingo-Morera, Agustin Roberto Garcia, Roger Borràs, Manuel López-Meseguer, Isabel Otero-González, Pilar Escribano-Subías, Joan Albert Barberà, Clara Martín-Ontiyuelo, and Isabel Blanco
- Subjects
medicine.medical_specialty ,business.industry ,Internal medicine ,cGMP-specific phosphodiesterase type 5 ,Cardiology ,medicine ,business - Published
- 2021
44. Systemic SP-A is increased in COVID-19 patients with abnormal diffusion capacity 6 months after hospital discharge
- Author
-
Rosa Faner, Lídia Perea Soriano, Oriol Vidal, Alvar Agusti, Tamara Cruz, Lidia Perea, Joan Albert Barberà, Nuria Albacar, Tamara García, Nuria Mendoza, Sandra Casas, Jacobo Sellares, Jorge Moisés, and Joan Ramon Badia
- Subjects
Coronavirus disease 2019 (COVID-19) ,business.industry ,Anesthesia ,Hospital discharge ,Medicine ,Diffusion (business) ,business - Published
- 2021
45. Lack of agreement between the exercise variables to assess the risk in PAH
- Author
-
Manuel López Meseguer, Víctor Manuel Mora Cuesta, Sergio Alcolea, Juan Antonio Domingo Morena, Joan Albert Barberà, Amaya Martínez Meñaca, Joaquín Rueda Soriano, Francisco Pastor Pérez, José Manuel Cifrián Martínez, and Pliar Escribano Subias
- Subjects
business.industry ,Environmental health ,Medicine ,business - Published
- 2021
46. Current Diagnostic and Prognostic Assessment of Pulmonary Hypertension
- Author
-
Subias, Pilar Escribano, Mir, Joan Albert Barberà, and Suberviola, Verónica
- Published
- 2010
- Full Text
- View/download PDF
47. 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
48. Therapeutic effects of soluble guanylate cyclase stimulation on pulmonary hemodynamics and emphysema development in guinea pigs chronically exposed to cigarette smoke
- Author
-
Isabel Blanco, Olga Tura-Ceide, Cristina Bonjoch, Tanja Paul, Victor I. Peinado, Valérie F E D Smolders, Daniel Aguilar, and Joan Albert Barberà
- Subjects
Pulmonary and Respiratory Medicine ,Physiology ,Hypertension, Pulmonary ,Vasodilator Agents ,Guinea Pigs ,Stimulation ,Pharmacology ,Pulmonary Disease, Chronic Obstructive ,Soluble Guanylyl Cyclase ,Animal model ,Smoke ,Physiology (medical) ,Tobacco ,Animals ,Medicine ,Cigarette smoke ,Lung ,Pulmonary hemodynamics ,COPD ,business.industry ,Therapeutic effect ,Hemodynamics ,Cell Biology ,medicine.disease ,Pulmonary hypertension ,Pulmonary Emphysema ,Guanylate Cyclase ,business ,Guanylate cyclase - Abstract
We have analyzed the effect of the soluble guanylate cyclase (sGC) stimulator BAY 41-2272 in a therapeutic intervention in guinea pigs chronically exposed to cigarette smoke (CS). The effects of sGC stimulation on respiratory function, pulmonary hemodynamics, airspace size, vessel remodeling, and inflammatory cell recruitment to the lungs were evaluated in animals that had been exposed to CS for 3 mo. CS exposure was continued for an additional 3 mo in half of the animals and withdrawn in the other half. Animals that stopped CS exposure had slightly lower pulmonary artery pressure (PAP) and right ventricle (RV) hypertrophy than those who continued CS exposure, but they did not recover from the emphysema and the inflammatory cell infiltrate. Conversely, oral BAY 41-2272 administration stopped progression or even reversed the CS-induced emphysema in both current and former smokers, respectively. Furthermore, BAY 41-2272 produced a reduction in the RV hypertrophy, which correlated with a decrease in the PAP values. By contrast, the degree of vessel remodeling induced by CS remained unchanged in the treated animals. Functional network analysis suggested perforin/granzyme pathway downregulation as an action mechanism capable of stopping the progression of emphysema after sGC stimulation. The pathway analysis also showed normalization of the expression of cGMP-dependent serine/kinases. In conclusion, in guinea pigs chronically exposed to CS, sGC stimulation exerts beneficial effects on the lung parenchyma and the pulmonary vasculature, suggesting that sGC stimulators might be a potential alternative for chronic obstructive pulmonary disease treatment that deserves further evaluation.
- Published
- 2019
49. Determinants of the Appearance and Progression of Early-Onset Chronic Obstructive Pulmonary Disease in Young Adults. A Case–Control Study With Follow-Up
- Author
-
Laura Vigil Giménez, Miguel Román Rodríguez, Judith Garcia-Aymerich, Diego Agustin Rodriguez Chiaradía, Joaquim Gea Guiral, Borja G. Cosío, Carlos J. Álvarez Martínez, Cristina Martínez-González, José Luis López-Campos, Pedro Jorge Marcos Rodríguez, Juan José Soler-Cataluña, Sergi Pascual-Guardia, Germán Peces-Barba, Joan Albert Barberà, en representación del Grupo Investigador del estudio Early Copd, Ciro Casanova Macario, Rosa Faner, Jesús Molina París, Alícia Borràs-Santos, Salud Santos-Pérez, Laura Carrasco Hernández, and Alvar Agusti
- Subjects
medicine.medical_specialty ,COPD ,education.field_of_study ,business.industry ,Population ,Case-control study ,General Medicine ,Disease ,medicine.disease ,Logistic regression ,respiratory tract diseases ,Pulmonary function testing ,03 medical and health sciences ,0302 clinical medicine ,030228 respiratory system ,Internal medicine ,Cohort ,medicine ,Young adult ,business ,education - Abstract
Introduction and objectives: Determinants of chronic obstructive pulmonary disease (COPD) in the early stages of its natural history are not well known. Improving our knowledge of these factors will help to design interventions that can modify prognosis. Study objectives are: a) to characterize a COPD population of young adults aged 35-50 years from a multidimensional point of view; b) to compare these patients with smokers with normal lung function: and c) to create a cohort of young adults aged 35-50 years (smokers or former smokers), with and without COPD, who will be followed in the future to improve understanding of the natural history of the disease. Participants and method: This is a case-control multicenter study aimed at establishing a well characterized cohort of young adults, smokers or former-smokers, with and without COPD, for subsequent follow-up. A total of 311 participants (101 cases and 210 controls) were selected from approximately 30 primary care settings and 12 hospitals in 8 Spanish regions. Subjects were smokers or former smokers (> 10 pack-years) aged 35-50 years. Diagnosis of COPD was based on a post-bronchodilator result of FEV1/FVC < 70%. The main study variables were: questionnaires on health, symptoms, exacerbations and daily physical activity, lung function tests, blood and sputum samples, and low-dose computed tomography. In the statistical analysis, COPD patient characteristics will be described and compared with control subjects using a logistic regression analysis. (C) 2018 SEPAR. Published by Elsevier Espana, S.L.U. All rights reserved.
- Published
- 2019
50. EARLY COPD: determinantes de la aparición y progresión de la enfermedad pulmonar obstructiva crónica en adultos jóvenes. Protocolo de un estudio caso-control con seguimiento
- Author
-
Joan Albert Barberà, Pedro Jorge Marcos Rodríguez, Laura Carrasco Hernández, Judith Garcia-Aymerich, Joaquim Gea Guiral, Laura Vigil Giménez, Juan José Soler-Cataluña, José Luis López-Campos, Rosa Faner, Carlos J. Álvarez Martínez, Alvar Agusti, Cristina Martínez-González, Borja G. Cosío, Ciro Casanova Macario, Alícia Borràs-Santos, Miguel Román Rodríguez, Jesús Molina París, Sergi Pascual-Guardia, Salud Santos-Pérez, Germán Peces-Barba, and Diego Agustin Rodriguez Chiaradía
- Subjects
Pulmonary and Respiratory Medicine ,03 medical and health sciences ,0302 clinical medicine ,030228 respiratory system ,business.industry ,Medicine ,business ,Humanities - Abstract
Resumen Introduccion y objetivos Los determinantes en fases iniciales de la historia natural de la enfermedad pulmonar obstructiva cronica (EPOC) son poco conocidos. Entenderlos mejor es de capital importancia para poder disenar intervenciones dirigidas a modificar su pronostico. Los principales objetivos del estudio son: a) caracterizar a una poblacion de adultos jovenes con EPOC de forma multidimensional; b) comparar estos pacientes con sujetos fumadores con funcion pulmonar normal; y c) establecer una cohorte de adultos jovenes con y sin EPOC, que pueda ser seguida a largo plazo para conocer mejor la historia natural de la enfermedad. Participantes y metodo EARLY COPD es un estudio multicentrico de casos y controles que permitira establecer una cohorte de sujetos para su seguimiento posterior. Se seleccionaron 311 (101 casos y 210 controles) participantes reclutados en una treintena de centros de atencion primaria y 12 hospitales de 8 comunidades autonomas espanolas. Los participantes eran fumadores o exfumadores (> 10 paquetes ano) de entre 35-50 anos de edad. Los casos presentaban una espirometria obstructiva con un FEV1/FVC
- Published
- 2019
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.