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Assessing Therapeutic Angiogenesis in a Murine Model of Hindlimb Ischemia
Published on: June 8, 2019
Bench-to-bedside review: Angiopoietin signalling in critical illness - a future target?
Matijs van Meurs1, Philipp Kümpers, Jack J M Ligtenberg
1Department of Critical Care, University Medical Center Groningen, University of Groningen, 9700RB Groningen, The Netherlands.
Abstract:
Multiple organ dysfunction syndrome (MODS) occurs in response to major insults such as sepsis, severe haemorrhage, trauma, major surgery and pancreatitis. The mortality rate is high despite intensive supportive care. The pathophysiological mechanism underlying MODS are not entirely clear, although several have been proposed. Overwhelming inflammation, immunoparesis, occult oxygen debt and other mechanisms have been investigated, and - despite many unanswered questions - therapies targeting these mechanisms have been developed. Unfortunately, only a few interventions, usually those targeting multiple mechanisms at the same time, have appeared to be beneficial. We clearly need to understand better the mechanisms that underlie MODS. The endothelium certainly plays an active role in MODS. It functions at the intersection of several systems, including inflammation, coagulation, haemodynamics, fluid and electrolyte balance, and cell migration. An important regulator of these systems is the angiopoietin/Tie2 signalling system. In this review we describe this signalling system, giving special attention to what is known about it in critically ill patients and its potential as a target for therapy.
Insights
Multiple organ dysfunction syndrome (MODS) is a critical condition with high mortality. Understanding the angiopoietin/Tie2 system
Area of Science:
- Critical care medicine
- Vascular biology
- Pathophysiology
Background:
- Multiple organ dysfunction syndrome (MODS) is a severe condition with high mortality, often resulting from sepsis, trauma, or surgery.
- The exact pathophysiological mechanisms of MODS remain unclear, despite research into inflammation, immunoparesis, and oxygen debt.
- The endothelium plays a crucial role in MODS, interfacing with inflammation, coagulation, and hemodynamic systems.
Purpose of the Study:
- To review the angiopoietin/Tie2 signalling system.
- To discuss the role of this system in critically ill patients.
- To explore the potential of angiopoietin/Tie2 as a therapeutic target for MODS.
Main Methods:
- Literature review focusing on the angiopoietin/Tie2 signalling pathway.
- Analysis of existing data on critically ill patients.
- Synthesis of information regarding endothelial function in MODS.
Main Results:
- The angiopoietin/Tie2 system is an important regulator of endothelial function.
- This system is implicated in the complex pathophysiology of MODS.
- Current understanding suggests potential therapeutic applications.
Conclusions:
- The angiopoietin/Tie2 signalling system is a key player in endothelial regulation during critical illness.
- Further research into this pathway may reveal novel therapeutic strategies for MODS.
- Targeting the angiopoietin/Tie2 system offers a promising avenue for improving outcomes in critically ill patients.
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