Circulating angiopoietin 2 correlates with mortality in a surgical population with acute lung injury/adult respiratory distress syndrome

Diana C. Gallagher, Samir M. Parikh, Konstantin Balonov, Andrew Miller, Shiva Gautam, Daniel Talmor, Vikas P. Sukhatme

Research output: Contribution to journalArticlepeer-review

112 Scopus citations

Abstract

There are few blood biomarkers predictive of mortality in adult respiratory distress syndrome (ARDS), and none that currently serve as therapeutic targets. Here, we ask whether a circulating protein angiopoietin 2 (Ang2) correlates with severity of lung injury and mortality in a surgical intensive care unit cohort with acute lung injury (ALI)/ARDS. Tie 2 is a tyrosine kinase receptor expressed on endothelial cells. One ligand, angiopoietin 1, phosphorylates Tie 2 and stabilizes adult vasculature. An alternate ligand, Ang2, serves as a context-dependent antagonist and disrupts barrier function. Previously, our laboratory detected high circulating Ang2 levels in septic patients and a correlation with low Pao2/Fio2. In this study, daily plasma was collected in 63 surgical intensive care unit patients. Eighteen patients met clinical criteria for ALI or ARDS. The median Ang2 at admission in patients who never developed ALI/ARDS was 3.7 ng/mL (interquartile range [IQR], 5.6; n = 45). The Ang2 on the day a patient met criteria for ALI/ARDS was 5.3 ng/mL (IQR, 6.7) for survivors (n = 11) and 19.8 ng/mL (IQR, 19.2) for nonsurvivors (n = 7; P = 0.004). To explore the mechanism of high Ang 2 leading to increased permeability, plasma from patients with ALI was applied to cultured lung endothelial cells and found to disrupt normal junctional architecture. This effect can be rescued with the Tie 2 agonist angiopoietin 1. A patient's convalescent (low Ang2) plasma did not disrupt junctional architecture. Although further studies with larger sample sizes will be needed to confirm these results, high Ang2 in critically ill patients with ALI/ARDS is associated with a poor outcome. These data, coupled with our cell culture experiments, suggest that antagonism of Ang2 may provide a future novel therapeutic target for ARDS.

Original languageEnglish (US)
Pages (from-to)656-661
Number of pages6
JournalShock
Volume29
Issue number6
DOIs
StatePublished - Jun 2008
Externally publishedYes

Keywords

  • ALI
  • ARDS
  • Angiopoietin
  • Endothelium
  • Surgical intensive care unit

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

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