Cardiovascular & Hematological Disorders-Drug Targets

(Formerly Current Drug Targets - Cardiovascular & Hematological Disorders)

Garry X. Shen  
University of Manitoba
Winnipeg, MB
Canada

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Cardiovascular Disease: What's All the AGE/RAGE About?

Author(s): Drazenka P. Barlovic, Merlin C. Thomas, Karin Jandeleit-Dahm.

Abstract:

Advanced glycation end-products (AGEs) are involved in mediating the effects of hyperglycaemia in diabetes. The most important receptor for AGEs is the receptor for advanced glycation end-products (RAGE). Binding of AGEs to RAGE converts transient cellular stimulation into sustained cellular dysfunction driven by long-term activation of the proinflammatory transcription factor NF-kB. Different splice variants of RAGE exist, including a soluble form that binds to AGEs but lacks the intracellular domain and thus fails to induce signal transduction. In this context, soluble RAGE may act as a therapeutic agent for AGE-induced effects. The balance between the synthesis of sRAGE and full-length RAGE may be an important determinant of AGE-induced dysfunction. An increasing amount of evidence suggests that AGEs either directly or via their interaction with RAGE play a pivotal role in the development and acceleration of atherosclerotic cardiovascular disease. These effects will be summarised in this review, together with the effects of therapeutic strategies targeting AGE/RAGE interactions. These treatments appear to have significant clinical potential, most likely in combination with currently used agents such as inhibitors of the renin-angiotensin system or statins, to reduce the major burden of diabetes, its associated cardiovascular disease.

Keywords: Advanced glycation, RAGE, cardiovascular disease, atherosclerosis, diabetes

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Article Details

VOLUME: 10
ISSUE: 1
Year: 2010
Page: [7 - 15]
Pages: 9
DOI: 10.2174/187152910790780050