First-hour circulating angiopoietin-2 concentrations were proportional to disease severity and predicted the future occurrence of shock or death (p < 0.0001) in patients with suspected infection.
Observational (n=270)
No
Does angiopoietin-2 contribute to adverse outcomes and mortality in sepsis?
Angiopoietin-2 induction contributes to adverse outcomes and mortality in sepsis, suggesting it as a potential therapeutic target and prognostic biomarker.
valor p: p=<0.0001
OBJECTIVE: : In sepsis, quiescent blood vessels become leaky and inflamed by mechanisms that are incompletely understood. We hypothesized that angiopoietin-2, a partial antagonist of the endothelium-stabilizing receptor Tie-2 secreted by endothelium, contributes to adverse outcomes in this disease. DESIGN: : Laboratory and animal research. SETTINGS: : Research laboratories and Emergency Department of Beth Israel Deaconess Medical Center, Boston, MA. SUBJECTS: : Angiopoietin-2 heterozygous mice, emergency department patients. MEASUREMENTS AND MAIN RESULTS: : Mice with one functional angiopoietin-2 allele developed milder kidney and lung injury, less tissue inflammation, and less vascular leakage compared to wild-type counterparts. Heterozygotes experienced >40% absolute survival advantage following two different models of sepsis (p = .004 and .018). In human subjects presenting to our emergency department with suspected infection (n = 270 combined), circulating angiopoietin-2 was markedly elevated within the first hour of clinical care. First-hour angiopoietin-2 concentrations were proportional to current disease severity (p < .0001), rose further over time in eventual nonsurvivors (p < .0001), and predicted the future occurrence of shock (p < .0001) or death (p < .0001) in the original cohort and an independent validation group. Finally, septic human serum disrupted the barrier function of microvascular endothelial cells, an effect fully neutralized by an angiopoietin-2 monoclonal antibody. CONCLUSIONS: : We conclude that angiopoietin-2 induction precedes and contributes to the adverse outcomes in sepsis, opening a new avenue for therapeutic investigation.
David et al. (Mon,) conducted a observational in Sepsis / suspected infection (n=270). Elevated circulating angiopoietin-2 vs. Lower circulating angiopoietin-2 was evaluated on Future occurrence of shock or death (p=<0.0001). First-hour circulating angiopoietin-2 concentrations were proportional to disease severity and predicted the future occurrence of shock or death (p < 0.0001) in patients with suspected infection.