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Circulating Cell Biomarkers in Pulmonary Arterial Hypertension: Relationship with Clinical Heterogeneity and Therapeutic Response Tura-Ceide, Olga Garcia-Lucio, Jéssica del Pozo, Roberto García, Agustín Roberto Ferrer, Elisabet Simeón Aznar, Carmen Pilar López Meseguer, Manuel Blanco, Isabel 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 Vall d'Hebron Barcelona Hospital Campus Hipertensió pulmonar - Tractament Marcadors bioquímics DISEASES::Respiratory Tract Diseases::Lung Diseases::Hypertension, Pulmonary::Familial Primary Pulmonary Hypertension ANATOMY::Cells::Epithelial Cells::Endothelial Cells Other subheadings::Other subheadings::Other subheadings::/metabolism CHEMICALS AND DRUGS::Biological Factors::Biomarkers ENFERMEDADES::enfermedades respiratorias::enfermedades pulmonares::hipertensión pulmonar::hipertensión pulmonar primaria familiar ANATOMÍA::células::células epiteliales::células endoteliales Otros calificadores::Otros calificadores::Otros calificadores::/metabolismo COMPUESTOS QUÍMICOS Y DROGAS::factores biológicos::biomarcadores 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). 2022-04-11T11:18:02Z 2022-04-11T11:18:02Z 2021-07 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Tura-Ceide O, Blanco I, Garcia-Lucio J, Del Pozo R, García AR, Ferrer E, et al. Circulating Cell Biomarkers in Pulmonary Arterial Hypertension: Relationship with Clinical Heterogeneity and Therapeutic Response. Cells. 2021 Jul;10(7):1688. 2073-4409 https://hdl.handle.net/11351/7348 10.3390/cells10071688 34359858 000677379200001 eng Cells;10(7) https://doi.org/10.3390/cells10071688 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess application/pdf application/pdf MDPI Scientia