The angiopoietin-Tie2 system as a therapeutic target in sepsis and acute lung injury.
BACKGROUND
Sepsis and acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) are life-threatening syndromes characterised by inflammation and increased vascular permeability. Amongst other factors, the angiopoietin-tyrosine kinase with immunoglobulin-like and EGF-like domains 2 (Tie2) system is involved.


OBJECTIVE
To explore whether the angiopoietin-Tie2 system provides suitable targets for the treatment of sepsis and ALI/ARDS.


METHODS
Original experimental and patient studies on angiopoietins and sepsis/endotoxemia, inflammation, lung injury, hyperpermeability, apoptosis, organ functions and vital outcomes were reviewed.


CONCLUSIONS
The angiopoietin-Tie2 system controls the responsiveness of the endothelium to inflammatory, hyperpermeability, apoptosis and vasoreactive stimuli. Angiopoietin-2 provokes inflammation and vascular hyperpermeability, while angiopoietin-1 has a protective effect. Targeted angiopoietin-2 inhibition with RNA aptamers or blocking antibodies is a potential anti-inflammatory and anti-vascular hyperpermeability strategy in the treatment of sepsis and ALI/ARDS.
van der Heijden
Melanie
M
VU University Medical Center, Institute for Cardiovascular Research, Department of Intensive Care, van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands. m.vanderheijden@vumc.nl
van Nieuw Amerongen
Geerten P
GP
Chedamni
Sunita
S
van Hinsbergh
Victor W M
VW
Johan Groeneveld
A B
AB
D055371:Acute Lung Injury / Q000188:drug therapy*; D042682:Angiopoietins / Q000037:antagonists & inhibitors* / Q000502:physiology; D006801:Humans; D042787:Receptor, TIE-2 / Q000187:drug effects* / Q000502:physiology; D018805:Sepsis / Q000188:drug therapy*
D042682:Angiopoietins; D042787:Receptor, TIE-2