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Pediatric Critical Care Medicine:
doi: 10.1097/PCC.0b013e3182917ccb
Feature Articles

Decreased Expression of Serum and Microvascular Vascular Endothelial Growth Factor Receptor-2 in Meningococcal Sepsis*

van der Flier, Michiel MD, PhD1,2; Baerveldt, Ewout M. MD3,4; Miedema, Annemieke MD5; Hartwig, Nico G. MD, PhD6; Hazelzet, Jan A. MD, PhD7; Emonts, Marieke MD, PhD6; de Groot, Ronald MD, PhD1,2; Prens, Errol P. MD, PhD3,4; van Vught, Adrianus J. MD, PhD5; Jansen, Nicolaas J. MD, PhD5

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Abstract

Objectives: To determine the skin microvessel expression of vascular endothelial growth factor receptor 2 and serum-soluble vascular endothelial growth factor receptor 2 levels in children with meningococcal sepsis.

Design: Observational study.

Setting: Two tertiary academic children hospital PICUs.

Patients: Children with meningococcal sepsis.

Intervention: Skin biopsy and blood sample collection.

Measurements and Main Results: Determination of skin microvessel vascular endothelial growth factor receptor 2 expression in skin biopsies by immunohistochemistry and measurement of serum-soluble vascular endothelial growth factor receptor 2 by enzyme-linked immunosorbent assay. Percentage of vascular endothelial growth factor receptor 2-positive skin microvessels and the staining intensity were significantly lower in children with meningococcal sepsis (n = 10) compared to controls (7.6% ± 8.8% vs 44.6% ± 39.2%; p = 0.009 and 0.7% ± 0.7% vs 1.7% ± 1.1%; p = 0.033, respectively). In addition, circulating serum levels of soluble vascular endothelial growth factor receptor 2 were decreased in sepsis (8,148 ± 1,140 pg/mL vs 13,414 ± 2,692 pg/mL; p < 0.001). Serum-soluble vascular endothelial growth factor receptor 2 levels (n = 28) were inversely correlated with Pediatric Risk of Mortality III score (r = –0.43; p = 0.023) and more decreased in nonsurvivors compared to survivors (5,640 ± 1,940 pg/mL vs 7,378 ± 2,336 pg/mL; p = 0.037).

Conclusions: Microvascular expression of vascular endothelial growth factor receptor 2 and serum-soluble vascular endothelial growth factor receptor 2 levels are decreased in children with sepsis. Serum-soluble vascular endothelial growth factor receptor 2 levels are inversely correlated with disease severity indicated by Pediatric Risk of Mortality III score and survival. Decreased vascular endothelial growth factor receptor 2 expression may hinder natural recovery from sepsis-associated microvascular injury and the effectiveness of therapeutic strategies targeting vascular endothelial growth factor-vascular endothelial growth factor receptor 2 signaling in sepsis patients.

©2013The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

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