Cardiovascular disease: What's all the AGE/RAGE about?

Drazenka P. Barlovic, Merlin C. Thomas, Karin Jandeleit-Dahm

Research output: Contribution to journalReview ArticleResearchpeer-review

28 Citations (Scopus)

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 pro-inflammatory 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.

Original languageEnglish
Pages (from-to)7-15
Number of pages9
JournalCardiovascular and Hematological Disorders - Drug Targets
Volume10
Issue number1
DOIs
Publication statusPublished - 1 Jan 2010
Externally publishedYes

Keywords

  • Advanced glycation
  • Atherosclerosis
  • Cardiovascular disease
  • Diabetes
  • RAGE

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