Circulating extracellular vesicles and neutrophil extracellular traps contribute to endothelial dysfunction in preeclampsia
Por:
Ramos A, Youssef L, Molina P, Torramadé-Moix S, Martinez-Sanchez J, Moreno-Castaño AB, Blasco M, Guillén-Olmos E, De Moner B, Pino M, Tortajada M, Camacho M, Borrell M, Crovetto F, Ramirez-Bajo MJ, Ventura-Aguiar P, Banon-Maneus E, Rovira J, Escolar G, Carreras E, Gratacós E, Diaz-Ricart M, Crispi F and Palomo M
Publicada:
13 dic 2024
Ahead of Print:
13 dic 2024
Resumen:
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.
Filiaciones:
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
:
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
Gratacós 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
Green Submitted, gold
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