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Absence of In Vivo Generalized Pro-Inflammatory Endothelial Activation in Severe, Early-Onset Preeclampsia

Departments of Obstetrics and Gynecology, Pathology and Laboratory Medicine, Medical Biology Section, Clinical Immunology, and Pathology, Groningen University Institute for Drug Exploration (GUIDE), University Medical Center Groningen, Groningen, The Netherlands r.b.donker{at}og/umcg.nl

Grietje Molema, PhD

Marijke M. Faas, PhD

Cees G.M. Kallenberg, MD, PhD

Maria G. van Pampus, MD, PhD

Albertus Timmer, MD, PhD

Jan G. Aarnoudse, MD, PhD

Departments of Obstetrics and Gynecology, Pathology and Laboratory Medicine, Medical Biology Section, Clinical Immunology, and Pathology, Groningen University Institute for Drug Exploration (GUIDE), University Medical Center Groningen, Groningen, The Netherlands

Objective: At present it is unclear whether endothelial activation is systematically present in preeclampsia or restricted to specialized vascular beds. Therefore, this study aimed to investigate the presence of generalized proinflammatory endothelial activation in severe, early-onset preeclampsia in vivo.

Methods: During caesarean section, biopsies were obtained from abdominal subcutaneous fat, abdominal fascia, and myometrium from 11 severe, early-onset preeclamptic and 19 healthy pregnant women. Prior to caesarean, section plasma levels of von Willebrand Factor (vWF), sVCAM-1, and C-reactive protein (CRP) were measured by ELISA. Consecutive cryostat sections were stained immunohistochemically for CD31, E-selectin, VCAM-1, and ICAM-1. For subcutaneous fat tissue, endothelial gene expression levels of E-selectin, VCAM-1, ICAM-1, endothelin-1 (ET-1), and endothelial nitric oxide synthase (eNOS) were quantified by real-time RT-PCR, using normalization to the endothelium-specific housekeeping genes CD31 and VE-cadherin.

Results: Plasma levels of vWF, sVCAM-1, and CRP were elevated in the preeclampsia group compared to the control group, indicating enhanced endothelial activation and inflammatory response in the severely diseased preeclamptic women. By immunohistochemical analysis, no E-selection and VCAM-1 expression could be detected in, and no differences in endothelial ICAM-1 staining could be observed between the preeclampsia and the control group for all tissues studied. Endothelial gene expression levels of E-selectin, VCAM-1, ICAM-1, ET-1, and eNOS were comparable between the preeclampsia and control group.

Conclusion: Protein and gene expression analysis of E-selectin, VCAM-1, ICAM-1, ET-1, and eNOS, key mediators involved in pro-inflammatory endothelial activation, could not identify endothelial activation in severe, early-onset preeclampsia in the tissues studies. However, elevated plasma levels of markers of endothelial activation and inflammation were observed. These results may suggest that in severe, early-onset preeclampsia pro-inflammatory endothelial cell activation is not a generalized phenomenon, but is likely restricted to (possibly organ-specific) specialized vascular beds.

Key Words: Preeclampsia • severe early-onset preeclampsia • endothelial activation • endothelial cell activation • pro-inflammatory endothelial activation • in vivo • protein expression • gene expression • vascular cell adhesion molecule-1 (VCAM-1) • intercellular adhesion molecule-1 (ICAM-1) • E-selectin • endothelial nitric oxide synthase (eNOS) • endothelin-1

Journal of the Society for Gynecologic Investigation, Vol. 12, No. 7, 518-528 (2005)
DOI: 10.1016/j.jsgi.2005.06.007


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