Circulating extracellular vesicles and neutrophil extracellular traps contribute to endothelial dysfunction in preeclampsia.

Autor:	Ramos A; Hemostasis and Erythropathology Laboratory, Hematopathology, Department of Pathology, Centre de Diagnòstic Biomèdic (CDB), Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain.; Barcelona Endothelium Team, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain., Youssef L; BCNatal | Barcelona Center for Maternal Fetal and Neonatal Medicine, Hospital Clínic and Hospital Sant Joan de Déu, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.; Josep Carreras Leukaemia Research Institute, Hospital Clinic/University of Barcelona Campus, Barcelona, Spain., Molina P; Hemostasis and Erythropathology Laboratory, Hematopathology, Department of Pathology, Centre de Diagnòstic Biomèdic (CDB), Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain., Torramadé-Moix S; Hemostasis and Erythropathology Laboratory, Hematopathology, Department of Pathology, Centre de Diagnòstic Biomèdic (CDB), Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain., Martinez-Sanchez J; Hemostasis and Erythropathology Laboratory, Hematopathology, Department of Pathology, Centre de Diagnòstic Biomèdic (CDB), Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain.; Barcelona Endothelium Team, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain., Moreno-Castaño AB; Hemostasis and Erythropathology Laboratory, Hematopathology, Department of Pathology, Centre de Diagnòstic Biomèdic (CDB), Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain., Blasco M; Nephrology and Kidney Transplant Department, Center of Reference in Complex Glomerular Disease (CSUR), Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain.; Red de Investigación Cooperativa Orientada a Resultados en Salud RICORS2040, Universidad Autónoma de Madrid, Madrid, Spain., Guillén-Olmos E; Nephrology and Kidney Transplant Department, Center of Reference in Complex Glomerular Disease (CSUR), Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain., De Moner B; Hemostasis and Erythropathology Laboratory, Hematopathology, Department of Pathology, Centre de Diagnòstic Biomèdic (CDB), Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain.; Barcelona Endothelium Team, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.; Josep Carreras Leukaemia Research Institute, Hospital Clinic/University of Barcelona Campus, Barcelona, Spain., Pino M; Hemostasis and Erythropathology Laboratory, Hematopathology, Department of Pathology, Centre de Diagnòstic Biomèdic (CDB), Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain., Tortajada M; BCNatal | Barcelona Center for Maternal Fetal and Neonatal Medicine, Hospital Clínic and Hospital Sant Joan de Déu, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain., Camacho M; BCNatal | Barcelona Center for Maternal Fetal and Neonatal Medicine, Hospital Clínic and Hospital Sant Joan de Déu, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain., Borrell M; BCNatal | Barcelona Center for Maternal Fetal and Neonatal Medicine, Hospital Clínic and Hospital Sant Joan de Déu, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain., Crovetto F; BCNatal | Barcelona Center for Maternal Fetal and Neonatal Medicine, Hospital Clínic and Hospital Sant Joan de Déu, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain., Ramirez-Bajo MJ; Laboratori Experimental de Nefrologia i Trasplantament (LENIT), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain., Ventura-Aguiar P; Nephrology and Kidney Transplant Department, Center of Reference in Complex Glomerular Disease (CSUR), Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain.; Laboratori Experimental de Nefrologia i Trasplantament (LENIT), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain., Banon-Maneus E; Laboratori Experimental de Nefrologia i Trasplantament (LENIT), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain., Rovira J; Laboratori Experimental de Nefrologia i Trasplantament (LENIT), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain., Escolar G; Hemostasis and Erythropathology Laboratory, Hematopathology, Department of Pathology, Centre de Diagnòstic Biomèdic (CDB), Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain., Carreras E; Barcelona Endothelium Team, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.; Josep Carreras Leukaemia Research Institute, Hospital Clinic/University of Barcelona Campus, Barcelona, Spain., Gratacos E; BCNatal | Barcelona Center for Maternal Fetal and Neonatal Medicine, Hospital Clínic and Hospital Sant Joan de Déu, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.; Centre for Biomedical Research on Rare Diseases (CIBER-ER), Instituto de Salud Carlos III, Madrid, Spain., Diaz-Ricart M; Hemostasis and Erythropathology Laboratory, Hematopathology, Department of Pathology, Centre de Diagnòstic Biomèdic (CDB), Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain.; Barcelona Endothelium Team, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain., Crispi F; BCNatal | Barcelona Center for Maternal Fetal and Neonatal Medicine, Hospital Clínic and Hospital Sant Joan de Déu, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.; Centre for Biomedical Research on Rare Diseases (CIBER-ER), Instituto de Salud Carlos III, Madrid, Spain., Palomo M; Barcelona Endothelium Team, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.; Hematology External Quality Assessment Laboratory, Biomedical Diagnostic Center, Hospital Clinic of Barcelona, Barcelona, Spain.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2024 Dec 13; Vol. 15, pp. 1488127. Date of Electronic Publication: 2024 Dec 13 (Print Publication: 2024).
DOI:	10.3389/fimmu.2024.1488127
Abstrakt:	Background: Preeclampsia (PE) is a pregnancy complication characterized by hypertension, proteinuria, endothelial dysfunction, and complement dysregulation. Placenta-derived extracellular vesicles (EVs), necessary in maternal-fetal communication, might contribute to PE pathogenesis. Moreover, neutrophil extracellular traps (NETs) play a pathogenic role in other complement-mediated pathologies, and their contribution in PE remains unexplored. Materials and Methods: EVs were isolated from PE (peEVs) and normotensive pregnant women sera. NETs were obtained incubating donor-pre-activated neutrophils with PE or control sera. Microvascular (HMEC) endothelial cells (ECs) were incubated with PE or control sera with or without (depleted sera) EVs or NETs, to assess changes in VCAM-1, ICAM-1, VE-cadherin, eNOS, VWF, ROS, and C5b-9 deposits. Results were expressed as fold increase vs. control. Results: VWF, VCAM-1, and ROS expression was significantly higher in cells exposed to PE sera vs. control (12.3 ± 8.1, 3.6 ± 2.3, and 1.8 ± 0.2, respectively, p < 0.05), though significantly lower in cells exposed to depleted PE (dPE) sera (6.1 ± 2.7, 0.7 ± 0.6, and 1.2 ± 0.1, respectively, vs. control, p < 0.05). EC exposure to depleted control sera supplemented with peEVs (dC+peEVs) significantly increased VWF, VCAM-1, and ROS compared to non-supplemented sera (4.5 ± 0.3, 2.8 ± 2.0, and 1.4 ± 0.2, respectively, p < 0.05). ICAM-1, VE-cadherin, and C5b-9 did not differ among groups. ECs incubated with PE-NETs increased VWF and VCAM-1 and decreased VE-cadherin expression vs. control (4 ± 1.6, 5.9 ± 1.2, and 0.5 ± 0.1, respectively, p < 0.05), and notably increased C5b-9 deposit (7.5 ± 2.9, p < 0.05). ICAM-1 and ROS did not differ. Conclusions: Both circulating EVs and NETs from PE pregnant women exhibit a deleterious effect on ECs. Whereas EVs trigger a pro-oxidant and proinflammatory state, NETs potentiate the activation of the complement system, as already described in PE. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Ramos, Youssef, Molina, Torramadé-Moix, Martinez-Sanchez, Moreno-Castaño, Blasco, Guillén-Olmos, De Moner, Pino, Tortajada, Camacho, Borrell, Crovetto, Ramirez-Bajo, Ventura-Aguiar, Banon-Maneus, Rovira, Escolar, Carreras, Gratacos, Diaz-Ricart, Crispi and Palomo.)
Databáze:	MEDLINE
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