PMID- 18091573
OWN - NLM
STAT- MEDLINE
DCOM- 20080909
LR  - 20211020
IS  - 1073-2322 (Print)
IS  - 1540-0514 (Electronic)
IS  - 1073-2322 (Linking)
VI  - 29
IP  - 6
DP  - 2008 Jun
TI  - Circulating angiopoietin 2 correlates with mortality in a surgical population 
      with acute lung injury/adult respiratory distress syndrome.
PG  - 656-61
AB  - 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.
FAU - Gallagher, Diana C
AU  - Gallagher DC
AD  - Division of Pulmonary, Critical Care, and Sleep Medicine, Beth Israel Deaconess 
      Medical Center, Boston, MA 02215, USA.
FAU - Parikh, Samir M
AU  - Parikh SM
FAU - Balonov, Konstantin
AU  - Balonov K
FAU - Miller, Andrew
AU  - Miller A
FAU - Gautam, Shiva
AU  - Gautam S
FAU - Talmor, Daniel
AU  - Talmor D
FAU - Sukhatme, Vikas P
AU  - Sukhatme VP
LA  - eng
GR  - R01 HL093234/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - Shock
JT  - Shock (Augusta, Ga.)
JID - 9421564
RN  - 0 (Angiopoietin-1)
RN  - 0 (Angiopoietin-2)
RN  - 0 (Biomarkers)
RN  - EC 2.7.10.1 (Receptor, TIE-2)
SB  - IM
MH  - Aged
MH  - Angiopoietin-1/blood
MH  - Angiopoietin-2/*blood
MH  - Biomarkers/blood
MH  - Critical Care
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Phosphorylation
MH  - Predictive Value of Tests
MH  - Receptor, TIE-2/metabolism
MH  - Respiratory Distress Syndrome/*blood/*mortality/surgery
PMC - PMC4037741
MID - NIHMS390294
COIS- These authors have not disclosed any commercial or other associations that might 
      pose a conflict of interest.
EDAT- 2007/12/20 09:00
MHDA- 2008/09/10 09:00
PMCR- 2014/05/29
CRDT- 2007/12/20 09:00
PHST- 2007/12/20 09:00 [pubmed]
PHST- 2008/09/10 09:00 [medline]
PHST- 2007/12/20 09:00 [entrez]
PHST- 2014/05/29 00:00 [pmc-release]
AID - 10.1097/shk.0b013e31815dd92f [doi]
PST - ppublish
SO  - Shock. 2008 Jun;29(6):656-61. doi: 10.1097/shk.0b013e31815dd92f.