Soluble forms of RAGE in human diseases: clinical and therapeutical implications.

Abstract

The ligand - receptor for advanced glycation end-products (RAGE) axis has emerged as a novel pathway involved in a wide spectrum of diseases, including diabetes mellitus, atherothrombosis, chronic renal failure, rheumatoid arthritis, neurodegeneration, cancer and aging. Circulating soluble forms of RAGE (sRAGE), arising from receptor ectodomain shedding and splice variant [endogenous secretory (es) RAGE] secretion, may counteract RAGE-mediated pathogenesis, by acting as a decoy. Several studies suggest that decreased levels of sRAGE and/or esRAGE may be useful as a biomarker of ligand-RAGE pathway hyperactivity and inadequate endogenous protective response, thus providing a powerful complement to cardiovascular risk stratification and an interesting target of therapeutic interventions. This review will focus on the pathophysiological determinants of soluble forms of RAGE in different clinical settings, with particular reference to the mechanisms involved in their generation and clearance, the association with cardiovascular risk factors, the interplay with low-grade inflammation, oxidative stress and endothelial dysfunction, and the possible pharmacological modulation of their plasma levels.

• Authors: Francesca Santilli, Natale Vazzana, Loredana G Bucciarelli, Giovanni Davì
• Journal: Current medicinal chemistry (Curr Med Chem) Vol. 16 Issue 8 Pg. 940-52 ( 2009) ISSN: 0929-8673 [Print] United Arab Emirates
• PMID: 19275604 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Receptor for Advanced Glycation End Products
• Receptors, Immunologic

Topics

• Diabetes Mellitus (metabolism)
• Disease
• Humans
• Molecular Biology
• Oxidative Stress
• Receptor for Advanced Glycation End Products
• Receptors, Immunologic (genetics, metabolism)
• Solubility