Soluble Forms of RAGE in Human Diseases: Clinical and Therapeutical Implications

Author(s): Francesca Santilli, Natale Vazzana, Loredana G. Bucciarelli, Giovanni Davi.

Journal Name: Current Medicinal Chemistry

Volume 16 , Issue 8 , 2009

Become EABM
Become Reviewer

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.

Keywords: Atherothrombosis, biomarker, diabetes mellitus, endogenous secretory RAGE, inflammation, oxidative stress, soluble RAGE

Rights & PermissionsPrintExport Cite as


Article Details

VOLUME: 16
ISSUE: 8
Year: 2009
Page: [940 - 952]
Pages: 13
DOI: 10.2174/092986709787581888
Price: $58

Article Metrics

PDF: 13