title: Fixing the leak: targeting the vascular endothelium in sepsis.
abstract: Angiopoietin-1 is a Tie-2 receptor agonist that stabilizes vascular endothelium, promoting endothelial maturation and preventing capillary leak. Angiopoietin-2 is largely a competitive partial antagonist that is markedly elevated in humans and animal models of sepsis and other inflammatory states, directly disrupts the endothelial barrier, and has been correlated with end-organ dysfunction and death in sepsis. In the previous issue of Critical Care, Alfieri and colleagues used intravital microscopy to study the microvasculature in a murine model of sepsis. Treatment with a modified angiopoietin-1 molecule led to reversal of albumin vascular leak and improved blood flow to skeletal muscle, as well as a decrease in the levels of several inflammatory cytokines. Importantly, the angiopoietin-1 variant was administered 20 hours after initial lipopolysaccharide challenge. This study adds to the evidence that the angiopoietin/Tie-2 axis represents a modifiable pathway through which targeted therapy may be able to directly reverse part of the pathology of sepsis.
authors.forename: Aaron
authors.initials: A
authors.lastname: Spicer
authors.forename: Carolyn S
authors.initials: CS
authors.lastname: Calfee
mesh_terms: D042683:Angiopoietin-1 / Q000008:administration & dosage* / Q000235:genetics*; D000818:Animals; D004195:Disease Models, Animal; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008297:Male; D008833:Microcirculation / Q000502:physiology*; D018805:Sepsis / Q000188:drug therapy* / Q000235:genetics*
chemical_list: D042683:Angiopoietin-1