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

Francesca Santilli1, Natale Vazzana, Loredana G Bucciarelli

  • 1Center of Excellence on Aging, "G. D'Annunzio" University Foundation, Chieti, Italy.

Current Medicinal Chemistry
|March 12, 2009
PubMed

Insights

Soluble forms of the Receptor for Advanced Glycation End-products (sRAGE) may act as a protective decoy. Lower sRAGE levels indicate pathway hyperactivity and could aid cardiovascular risk assessment.

Area of Science:

  • Biomedical Science
  • Pathophysiology
  • Molecular Biology

Background:

  • The Receptor for Advanced Glycation End-products (RAGE) pathway is implicated in diverse diseases like diabetes, neurodegeneration, and cancer.
  • Soluble RAGE (sRAGE) and endogenous secretory RAGE (esRAGE) may act as decoys, counteracting RAGE-mediated pathogenesis.
  • Decreased sRAGE/esRAGE levels are linked to RAGE pathway hyperactivity and insufficient endogenous protection.

Purpose of the Study:

  • To review the pathophysiological determinants of soluble RAGE forms in various clinical settings.
  • To explore mechanisms of sRAGE generation and clearance.
  • To examine the association of sRAGE with cardiovascular risk, inflammation, oxidative stress, and endothelial dysfunction.

Main Methods:

  • Literature review focusing on pathophysiological determinants.
  • Analysis of mechanisms for sRAGE generation and clearance.
  • Examination of sRAGE associations with clinical factors and potential therapeutic modulation.

Main Results:

  • Soluble RAGE forms (sRAGE, esRAGE) function as decoys against RAGE-mediated disease.
  • Reduced sRAGE levels may serve as biomarkers for RAGE pathway overactivity.
  • sRAGE levels correlate with cardiovascular risk factors, inflammation, oxidative stress, and endothelial dysfunction.

Conclusions:

  • Soluble RAGE forms are critical in counteracting RAGE-axis related diseases.
  • sRAGE/esRAGE levels are potential biomarkers for disease activity and cardiovascular risk.
  • Pharmacological modulation of plasma sRAGE levels presents a therapeutic target.

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