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

Abstract

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.

Keywords::

• acute lung injury
• acute respiratory distress syndrome
• angiopoietin
• critical care
• inflammation
• intensive care unit
• leakage
• permeability
• sepsis
• Tie1
• Tie2

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