Vascular Endothelial Growth Factor Is Increased During the First 48 Hours of Human Septic Shock and Correlates With Vascular Permeability

Abstract

Meningococcal septic shock is an important cause of morbidity and mortality in children and young adults worldwide and is the prototypical gram-negative septic shock. One of the key factors in the development of shock is increased microvascular permeability. Vascular endothelial growth factor (VEGF) is a central factor in angiogenesis and is an important mediator of vascular permeability. Thirteen patients with meningococcal infection (eight presenting with shock) were investigated in the early phase of invasive meningococcal disease. Cytokines, complement activation, and VEGF plasma concentrations were measured during the first 48 h on the pediatric intensive care unit. Increased cytokine concentrations and activation of the complement system were observed. VEGF plasma concentrations were increased (median 193 pg/mL, range 71-1082) and were highest in the presence of shock (208 pg/mL, 169-1082) compared with patients presenting without shock (92 pg/mL range 71-299). VEGF concentration at admission correlated with the severity of disease (pediatric risk of mortality score, R=0.90 [Spearman], P=0.0001) and the amount of fluids administered within the first 24 h (R=0.90, P<0.0001). In all patients, a decrease in VEGF was associated with a decrease in fluid intake during t=24 to 48 h. The results suggest that apart from correlation with IL-1 beta, -10, -12, and complement activation, microvascular permeability in sepsis is also closely linked to the plasma concentration of VEGF. The role of VEGF in sepsis-associated increased microvascular permeability needs further exploration and may represent a new therapeutic target.

Angiopoietin-2, Marker and Mediator of Endothelial Activation With Prognostic Significance Early After Trauma?

“…For example, plasma levels of VEGF have been shown to be increased in septic patients and were related to disease severity and mortality. 39,40 In contrast in the present study, plasma VEGF levels measured 30 min after injury were unrelated to injury severity, systemic hypoperfusion and patient outcome. This finding is in accordance with previously published studies on trauma and burn patients where VEGF levels on admission were unrelated to the extent of the initial injury and not different from a healthy control group.…”

The Increase of Endothelial Progenitor Cells in the Peripheral Blood: A New Parameter for Detecting Onset and Severity of Sepsis

“…In this light, two independent studies report an association between human severe sepsis/septic shock and elevated circulating levels of VEGF (26)(27). In particular Yano et a!., in a human endotoxemia model, revealed a significant increase of VEGF as early as 4 hrs from inoculation of LPS.…”

Vascular Endothelial Growth Factor (VEGF) Receptor-2 Tyrosine 1175 Signaling Controls VEGF-induced von Willebrand Factor Release from Endothelial Cells via Phospholipase C-γ1- and Protein Kinase A-dependent Pathways

“…VEGF is well expressed in the chronic inflammatory skin disease, psoriasis, and in synovial fluid in rheumatoid arthritis (9 -12). In addition, previous studies found an association between human severe sepsis/septic shock with elevated circulating levels of VEGF and PlGF (13,14). Using an in vitro monocyte migration assay and in vivo mouse models of arthritis, several groups, including ours, have suggested that one mechanism by which VEGF causes inflammation is by modulating the infiltration and secretion of monocytes/macrophages via the activation of VEGFR1 (11,12,15).…”