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Article

Circulating Cell Biomarkers in Pulmonary Arterial Hypertension: Relationship with Clinical Heterogeneity and Therapeutic Response

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Department of Pulmonary Medicine, Hospital Clínic-Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Spain
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Biomedical Research Networking Centre on Respiratory Diseases (CIBERES), 28029 Madrid, Spain
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Girona Biomedical Research Institute (IDIBGI), 17190 Girona, Spain
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Flow Cytometry and Cell Sorting Facility, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain
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Pulmonology Department, Hospital del Mar, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain
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Unitat de Malaties Autoimmunes Sistèmiques. Servei de Medicina Interna Hospital Universitari Vall d’Hebron, Departament de Medicina, Universitat Autònoma de Barcelona, 08035 Barcelona, Spain
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Servei de Pneumologia, Hospital Universitari Vall d’Hebron, Departament de Medicina, Universitat Autònoma de Barcelona, 08035 Barcelona, Spain
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Authors to whom correspondence should be addressed.
Academic Editor: Rozenn Quarck
Cells 2021, 10(7), 1688; https://doi.org/10.3390/cells10071688
Received: 30 April 2021 / Revised: 21 June 2021 / Accepted: 28 June 2021 / Published: 4 July 2021
(This article belongs to the Special Issue Cellular Pathogenesis of Pulmonary Arterial Hypertension)
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+CD42bCD62E+), 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. View Full-Text
Keywords: pulmonary arterial hypertension; endothelial dysfunction; biomarkers; progenitor cells; endothelial extracellular vesicles; PAH-specific treatment pulmonary arterial hypertension; endothelial dysfunction; biomarkers; progenitor cells; endothelial extracellular vesicles; PAH-specific treatment
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MDPI and ACS Style

Tura-Ceide, O.; Blanco, I.; Garcia-Lucio, J.; del Pozo, R.; García, A.R.; Ferrer, E.; Crespo, I.; Rodríguez-Chiaradia, D.A.; Simeon-Aznar, C.P.; López-Meseguer, M.; Martín-Ontiyuelo, C.; Peinado, V.I.; Barberà, J.A. Circulating Cell Biomarkers in Pulmonary Arterial Hypertension: Relationship with Clinical Heterogeneity and Therapeutic Response. Cells 2021, 10, 1688. https://doi.org/10.3390/cells10071688

AMA Style

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, Barberà JA. Circulating Cell Biomarkers in Pulmonary Arterial Hypertension: Relationship with Clinical Heterogeneity and Therapeutic Response. Cells. 2021; 10(7):1688. https://doi.org/10.3390/cells10071688

Chicago/Turabian Style

Tura-Ceide, Olga, 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. 2021. "Circulating Cell Biomarkers in Pulmonary Arterial Hypertension: Relationship with Clinical Heterogeneity and Therapeutic Response" Cells 10, no. 7: 1688. https://doi.org/10.3390/cells10071688

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