Soluble forms of RAGE in human diseases: Clinical and therapeutical implications

Francesca Santilli, Natale Vazzana, Loredana G. Bucciarelli, Giovanni Davì

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)940-952
Number of pages13
JournalCurrent Medicinal Chemistry
Volume16
Issue number8
DOIs
Publication statusPublished - 2009

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Keywords

  • Atherothrombosis
  • Biomarker
  • Diabetes mellitus
  • Endogenous secretory RAGE
  • Inflammation
  • Oxidative stress
  • Soluble RAGE

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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