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

Expert Opin Ther Targets

VU University Medical Center, Institute for Cardiovascular Research, Department of Intensive Care, van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.

Published: January 2009

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.

Results/conclusion: 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.

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http://dx.doi.org/10.1517/14728220802626256DOI Listing

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