Open AccessCIRCULATING ANGIOPOIETIN 2 CORRELATES WITH MORTALITY IN A SURGICAL POPULATION WITH ACUTE LUNG INJURY/ADULT RESPIRATORY DISTRESS SYNDROME
Author(s) -
Diana Gallagher,
Samir M. Parikh,
Konstantin Balonov,
Andrew C. Miller,
Shiva Gautam,
Daniel Talmor,
Vikas P. Sukhatme
Publication year - 2008
Publication title -
shock
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.095
H-Index - 117
eISSN - 1540-0514
pISSN - 1073-2322
DOI - 10.1097/shk.0b013e31815dd92f
Subject(s) - ards , medicine , interquartile range , intensive care unit , angiopoietin receptor , angiopoietin , lung , intensive care , context (archaeology) , population , gastroenterology , respiratory distress , surgery , receptor , intensive care medicine , vascular endothelial growth factor , biology , paleontology , environmental health , vegf receptors
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 Pa(O2)/F(IO2). 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.