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.
Center of Excellence on Aging, “G. D'Annunzio” University Foundation, Via Colle dell'Ara, 66013 Chieti, Italy.
Publication date: March 1, 2009
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Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.