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.
Highlights
Angiopoietin-1 is a Tie-2 receptor agonist that stabilizes vascular endothelium, promoting endothelial maturation and preventing capillary leak
Alternative approaches to effective delivery of Ang-1 have been investigated in experimental models
Ang-1 reduced tumor necrosis factor alpha, interferon gamma, triggering receptor expressed on myeloid cells-1, granulocyte colony-stimulating factor, and IL-10 in LPSunchallenged mice, a novel finding given that other studies have not treated well mice with Tie-2 agonists
Summary
Angiopoietin-1 is a Tie-2 receptor agonist that stabilizes vascular endothelium, promoting endothelial maturation and preventing capillary leak. Alternative approaches to effective delivery of Ang-1 have been investigated in experimental models. Cartilage oligomeric matrix protein-angiopoietin-1 (COMP.Ang-1) is a soluble and stabilized variant that binds more avidly to Tie-2 than native Ang-1 [12].
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