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.
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.
Authors: Heming Wang; Brian E Cade; Han Chen; Kevin J Gleason; Richa Saxena; Tao Feng; Emma K Larkin; Ramachandran S Vasan; Honghuang Lin; Sanjay R Patel; Russell P Tracy; Yongmei Liu; Daniel J Gottlieb; Jennifer E Below; Craig L Hanis; Lauren E Petty; Shamil R Sunyaev; Alexis C Frazier-Wood; Jerome I Rotter; Wendy Post; Xihong Lin; Susan Redline; Xiaofeng Zhu Journal: Hum Mol Genet Date: 2016-12-01 Impact factor: 6.150
Authors: V Fehring; U Schaeper; K Ahrens; A Santel; O Keil; M Eisermann; K Giese; Jörg Kaufmann Journal: Mol Ther Date: 2014-01-06 Impact factor: 11.454
Authors: Vijay C Ganta; Walter Cromer; Ginny L Mills; James Traylor; Merilyn Jennings; Sarah Daley; Benjamin Clark; J Michael Mathis; Michael Bernas; Moheb Boktor; Paul Jordan; Marlys Witte; J Steven Alexander Journal: Inflamm Bowel Dis Date: 2010-06 Impact factor: 5.325
Authors: Melanie van der Heijden; Peter Pickkers; Geerten P van Nieuw Amerongen; Victor W M van Hinsbergh; Martijn P W J M Bouw; Johannes G van der Hoeven; A B Johan Groeneveld Journal: Intensive Care Med Date: 2009-06-24 Impact factor: 17.440