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

Abstract

To measure plasma levels of angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), and vascular endothelial growth factor (VEGF) early after trauma and to determine their clinical significance. Angiopoietins and VEGF play a central role in the physiology and pathophysiology of endothelial cells. Ang-2 has recently been shown to have pathogenetic significance in sepsis and acute lung injury. Little is known about the role of angiopoietins and VEGF early after trauma. Blood specimens from consecutive major trauma patients were obtained immediately upon arrival in the emergency department and plasma samples assayed for Ang-1, Ang-2, VEGF, markers of endothelial activation, protein C pathway, fibrinolytic system, and complement. Base deficit was used as a measure of tissue hypoperfusion. Data were collected prospectively. Blood samples were obtained from 208 adult trauma patients within 30 minutes after injury before any significant fluid resuscitation. Plasma levels of Ang-2, but not Ang-1 and VEGF were increased and correlated independently with severity of injury and tissue hypoperfusion. Furthermore, plasma levels of Ang-2 correlated with markers of endothelial activation, coagulation abnormalities, and activation of the complement cascade and were associated with worse clinical outcome. Ang-2 is released early after trauma with the degree proportional to both injury severity and systemic hypoperfusion. High levels of Ang-2 were associated with an activated endothelium, coagulation abnormalities, complement activation, and worse clinical outcome. These data indicate that Ang-2 is a marker and possibly a direct mediator of endothelial activation and dysfunction after severe trauma.