Fixing the leak: targeting the vascular endothelium in sepsis
1 Department of Pediatrics, University of California, San Francisco, San Francisco, CA 94143, USA
2 Departments of Anesthesia and Medicine, University of California, San Francisco, San Francisco, CA 94143, USA
Critical Care 2012, 16:177 doi:10.1186/cc11829
See related research by Alfieri et al., http://ccforum.com/content/16/5/R182Published: 21 November 2012
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.