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The RAGE axis in systemic inflammation, acute lung injury and myocardial dysfunction: An important therapeutic target?

Creagh-Brown, Benedict C., Quinlan, Gregory J., Evans, Timothy W. and Burke-Gaffney, Anne (2010) The RAGE axis in systemic inflammation, acute lung injury and myocardial dysfunction: An important therapeutic target? Intensive Care Medicine, 36 (10). pp. 1644-1656.

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Abstract

Background: The sepsis syndromes, frequently complicated by pulmonary and cardiac dysfunction, remain a major cause of death amongst the critically ill. Targeted therapies aimed at ameliorating the systemic inflammation that characterises the sepsis syndromes have largely yielded disappointing results in clinical trials. Whilst there are many potential reasons for lack of success of clinical trials, one possibility is that the pathways targeted, to date, are only modifiable very early in the course of the illness. More recent approaches have therefore attempted to identify pathways that could offer a wider therapeutic window, such as the receptor for advanced glycation end-products (RAGE) and its ligands.

Purpose: The objectives of this study were to review the evidence supporting the role of the RAGE axis in systemic inflammation and associated acute lung injury and myocardial dysfunction, to explore some of the problems and conflicts that these RAGE studies have raised and to consider strategies by which they might be resolved.

Methods: MEDLINE was searched (1990-2010) and relevant literature collected and reviewed.

Results and conclusion: RAGE is an inflammation-perpetuating receptor with a diverse range of ligands. Evidence supporting a role of the RAGE axis in the pathogenesis of systemic inflammation, ALI and myocardial dysfunction is compelling with numerous animal experiments showing the beneficial effects of inhibiting the RAGE axis. Despite a number of unanswered questions that need to be further addressed, the potential for inhibiting RAGE-mediated inflammation in humans undoubtedly exists.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
NameEmailORCID
Creagh-Brown, Benedict C.b.creagh-brown@surrey.ac.uk
Quinlan, Gregory J.
Evans, Timothy W.
Burke-Gaffney, Anne
Date : 15 July 2010
DOI : 10.1007/s00134-010-1952-z
Uncontrolled Keywords : RAGE; SIRS; Sepsis; ALI; ARDS; Myocardial dysfunction; HMGB1
Depositing User : Clive Harris
Date Deposited : 20 Mar 2019 11:37
Last Modified : 20 Mar 2019 12:08
URI: http://epubs.surrey.ac.uk/id/eprint/850772

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