Role of Angiopoietin/Tie2 in Critical Illness: Promising Biomarker, Disease Mediator, and Therapeutic Target?

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 a...

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Main Authors: Alexander Lukasz, Philipp Kümpers, Sascha David
Format: Article
Language:English
Published: Wiley 2012-01-01
Series:Scientifica
Online Access:http://dx.doi.org/10.6064/2012/160174
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author Alexander Lukasz
Philipp Kümpers
Sascha David
author_facet Alexander Lukasz
Philipp Kümpers
Sascha David
author_sort Alexander Lukasz
collection DOAJ
description 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.
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spelling doaj-art-ea86a32ae0d5466596e72af2e24052112025-08-20T02:22:02ZengWileyScientifica2090-908X2012-01-01201210.6064/2012/160174160174Role of Angiopoietin/Tie2 in Critical Illness: Promising Biomarker, Disease Mediator, and Therapeutic Target?Alexander Lukasz0Philipp Kümpers1Sascha David2Department of Nephrology & Hypertension, Hannover Medical School, Carl-Neuberg Straße 1, 30625 Hannover, GermanyDepartment of Internal Medicine, Rheumatology and Nephrology, University Hospital Münster, 48149Münster, GermanyDepartment of Nephrology & Hypertension, Hannover Medical School, Carl-Neuberg Straße 1, 30625 Hannover, GermanyCritical 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.http://dx.doi.org/10.6064/2012/160174
spellingShingle Alexander Lukasz
Philipp Kümpers
Sascha David
Role of Angiopoietin/Tie2 in Critical Illness: Promising Biomarker, Disease Mediator, and Therapeutic Target?
Scientifica
title Role of Angiopoietin/Tie2 in Critical Illness: Promising Biomarker, Disease Mediator, and Therapeutic Target?
title_full Role of Angiopoietin/Tie2 in Critical Illness: Promising Biomarker, Disease Mediator, and Therapeutic Target?
title_fullStr Role of Angiopoietin/Tie2 in Critical Illness: Promising Biomarker, Disease Mediator, and Therapeutic Target?
title_full_unstemmed Role of Angiopoietin/Tie2 in Critical Illness: Promising Biomarker, Disease Mediator, and Therapeutic Target?
title_short Role of Angiopoietin/Tie2 in Critical Illness: Promising Biomarker, Disease Mediator, and Therapeutic Target?
title_sort role of angiopoietin tie2 in critical illness promising biomarker disease mediator and therapeutic target
url http://dx.doi.org/10.6064/2012/160174
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