• Expert Opin. Ther. Targets · Jan 2009

    Review

    The angiopoietin-Tie2 system as a therapeutic target in sepsis and acute lung injury.

    • Melanie van der Heijden, Geerten P van Nieuw Amerongen, Sunita Chedamni, Victor W M van Hinsbergh, and A B Johan Groeneveld.
    • 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
    • Expert Opin. Ther. Targets. 2009 Jan 1;13(1):39-53.

    BackgroundSepsis 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.ObjectiveTo explore whether the angiopoietin-Tie2 system provides suitable targets for the treatment of sepsis and ALI/ARDS.MethodsOriginal experimental and patient studies on angiopoietins and sepsis/endotoxemia, inflammation, lung injury, hyperpermeability, apoptosis, organ functions and vital outcomes were reviewed.Results/ConclusionThe 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.

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