title: Role of angiopoietin/tie2 in critical illness: promising biomarker, disease mediator, and therapeutic target?
abstract: Critical illness is a descriptive, broad term for a serious clinical condition that can result from enormously heterogeneous etiologies. A common end feature these patients regularly suffer from is the so-called multiple organ dysfunction syndrome (MODS), often a consequence of organ hypoperfusion and ischemia, coagulopathies, overwhelming inflammatory responses, immune paralysis and mitochondrial dysfunction. Mechanistically, endothelial injury and particularly microvascular leakage is a major step in the pathophysiology of MODS and contributes to its mortality. The angiopoietin (Angpt)/Tie2 system consists of the endothelial tyrosine kinase Tie2 and its 4 circulating ligands (Angpt1-4). The balance between the agonistic ligand "Angpt-1" and the antagonistic one "Angpt-2" regulates baseline endothelial barrier function and its response to injury and is therefore considered a gatekeeper of endothelial activation. This paper provides a systematic overview of the Angpt/Tie2 system with respect to (1) its role as a global biomarker of endothelial activation in critical ill patients, (2) its contribution to MODS pathophysiology as a disease mediator, and last but not least (3) putative therapeutic applications to modify the activation state of Tie2 in mice and men.
authors.affiliation: Department of Nephrology & Hypertension, Hannover Medical School, Carl-Neuberg Straße 1, 30625 Hannover, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Lukasz
authors.forename: Philipp
authors.initials: P
authors.lastname: Kümpers
authors.forename: Sascha
authors.initials: S
authors.lastname: David