Circulating Cell Biomarkers in Pulmonary Arterial Hypertension : Relationship with Clinical Heterogeneity and Therapeutic Response
Tura-Ceide, Olga (Hospital Clínic i Provincial de Barcelona)
Blanco, Isabel (Hospital Clínic i Provincial de Barcelona)
Garcia-Lucio, Jéssica (Hospital Clínic i Provincial de Barcelona)
del Pozo, Roberto (Hospital Clínic i Provincial de Barcelona)
García, Agustín Roberto (Hospital Clínic i Provincial de Barcelona)
Ferrer, Elisabet (Hospital Clínic i Provincial de Barcelona)
Crespo García, Isabel (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Rodríguez-Chiaradia, Diego A. (Hospital del Mar (Barcelona, Catalunya))
Simeón-Aznar, Carmen Pilar (Universitat Autònoma de Barcelona. Departament de Medicina)
López-Meseguer, Manuel (Universitat Autònoma de Barcelona. Departament de Medicina)
Martín-Ontiyuelo, Clara (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Peinado, Víctor I. (Hospital Clínic i Provincial de Barcelona)
Barberà i Mir, Joan Albert (Hospital Clínic i Provincial de Barcelona)

Data:	2021
Resum:	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 + CD45 low) 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.
Ajuts:	Ministerio de Economía y Competitividad PI12/00510 Ministerio de Economía y Competitividad PI15/00582 Instituto de Salud Carlos III PI18/00960 Instituto de Salud Carlos III CP17/00114
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Pulmonary arterial hypertension ; Endothelial dysfunction ; Biomarkers ; Progenitor cells ; Endothelial extracellular vesicles ; PAH-specific treatment
Publicat a:	Cells, Vol. 10 (july 2021) , ISSN 2073-4409

DOI: 10.3390/cells10071688
PMID: 34359858

15 p, 1.2 MB

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