Endothelial damage and complement dysregulation in fetuses from pregnancies complicated by preeclampsia
Por:
Ramos A, Youssef L, Molina P, Martinez-Sanchez J, Moreno-Castaño AB, Blasco M, De Moner B, Tortajada M, Camacho M, Borrell M, Crovetto F, Pino M, Escolar G, Carreras E, Gratacós E, Diaz-Ricart M, Palomo M and Crispi F
Publicada:
1 may 2025
Ahead of Print:
1 feb 2025
Resumen:
IntroductionOur objective was to evaluate the endothelial function profile and complement system in fetuses from preeclamptic pregnancies using ex vivo and in vitro approaches. Material and MethodsA total of 66 singleton pregnancies were prospectively recruited comprising 34 cases of preeclampsia and 32 normotensive pregnancies matched for baseline characteristics. In the ex vivo approach, soluble tumor necrosis factor-a receptor 1 (sTNFR1), vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1), Von Willebrand factor (sVWF), terminal complement complex (sC5b-9), Factor H, complement component C3a and Factor Bb were analyzed in fetal cord blood samples. In the in vitro model, vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), Von Willebrand factor (VWF), vascular endothelial cadherin (VE-Cadherin), endothelial nitric oxide synthase (eNOS), reactive oxygen species (ROS) and C5b-9 deposits were evaluated on endothelial cells in culture exposed to fetal sera or plasma. ResultsIncreased sVCAM-1, sICAM- l and decreased Factor H and Factor Bb concentrations were detected in preeclampsia fetuses as compared to fetuses from normotensive mothers (509.4 +/- 28 vs. 378.4 +/- 34.3 ng/mL, 161.1 +/- 11.9 vs. 114.8 +/- 6.8, 199.6 +/- 18.3 vs. 267.1 +/- 15.4 ng/mL and 6.6 +/- 0.7 vs. 10.3 +/- 1.4 mu g/mL respectively, p < 0.05) with similar results in sTNFR1, sVWF, sC5b-9 and C3a. Endothelial cells exposed to fetal sera from preeclampsia showed incremented expression of VCAM-1(38.1 +/- 1.4% vs. 28.3 +/- 1.6%, p < 0.01), ICAM-1 (12 +/- 0.9% vs. 8.6 +/- 0.6%, p < 0.05), VWF (43.5 +/- 2.9% vs. 3.7 +/- 0.3%, p < 0.05), and ROS (5 x 1013 +/- 1 x 1012 vs. 3.5 x 1013 +/- 1.4 x 1012, p < 0.01) with similar expression of VE-Cadherin and eNOS as compared to those exposed to control fetuses. While soluble C5b-9 was similar between the study groups (851.4 +/- 177.5 vs. 751.4 +/- 132.81 ng/mL, p > 0.05), significantly less C5b-9 deposits on endothelial cells were induced by fetal plasma from preeclamptic compared to normotensive mothers (fold change 0.08 +/- 0.02 vs. 0.48 +/- 0.13, p < 0.01). ConclusionsHigh levels of endothelial adhesion molecules and oxidative stress products suggest endothelial damage and reduced in vitro deposition of C5b-9 indicates complement dysregulation in preeclampsia fetuses. More research is necessary to study the impact of preeclampsia on fetal vascular health and innate immunity.
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, Barcelona, Spain
:
BCNatal | Barcelona Center for Maternal Fetal and Neonatal Medicine, Hospital Clínic and Hospital Sant Joan de Déu, 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
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, 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
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, Barcelona, Spain
Josep Carreras Leukaemia Research Institute, Hospital Clinic/University of Barcelona Campus, Barcelona, Spain
Tortajada M:
BCNatal | Barcelona Center for Maternal Fetal and Neonatal Medicine, Hospital Clínic and Hospital Sant Joan de Déu, 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, 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, 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, IDIBAPS, University of Barcelona, 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
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, 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, IDIBAPS, University of Barcelona, Barcelona, Spain
Centre for Biomedical Research on Rare Diseases (CIBER-ER), 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, Barcelona, Spain
Palomo M:
Barcelona Endothelium Team, Barcelona, Spain
Hematology External Quality Assessment Laboratory, Biomedical Diagnostic Center, Hospital Clinic of Barcelona, Barcelona, Spain
Crispi F:
BCNatal | Barcelona Center for Maternal Fetal and Neonatal Medicine, Hospital Clínic and Hospital Sant Joan de Déu, IDIBAPS, University of Barcelona, Barcelona, Spain
Centre for Biomedical Research on Rare Diseases (CIBER-ER), Madrid, Spain
Green Submitted, gold
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