RAGE: A novel target for drug intervention in diabetic vascular disease

Barry I. Hudson, Ann Marie Schmidt

Research output: Contribution to journalReview articlepeer-review

71 Scopus citations

Abstract

At high levels as seen in diabetes, glucose reacts with and forms adducts (advanced glycation end products; AGEs) on macromolecules including proteins and DNA, eliciting cellular dysfunction and leading to vascular disease. The major means is through cellular receptors; the best characterized is the receptor for advanced glycation end products (RAGE). Accumulation of both AGE/RAGE in addition to other identified ligands of RAGE, including S100/calgranulins, is the hallmark of this receptor in disease pathogenesis. Blockade of ligand-receptor interaction directly at the protein level, or transgenetically, prevents development of micro vascular (nephropathy) and macro vascular (atherosclerosis/restenosis) disease in small animal models. Furthermore, allelic variants of RAGE exist that alter the protein function and gene expression, which may further affect disease outcome. In conclusion, RAGE is a target for drug development to prevent vascular disease in diabetic and nondiabetic subjects.

Original languageEnglish (US)
Pages (from-to)1079-1086
Number of pages8
JournalPharmaceutical Research
Volume21
Issue number7
DOIs
StatePublished - Jul 1 2004
Externally publishedYes

Keywords

  • advanced glycation end products
  • diabetes
  • immunoglobulin receptor
  • nephropathy
  • polymorphism
  • restenosis
  • vascular disease

ASJC Scopus subject areas

  • Chemistry(all)
  • Pharmaceutical Science
  • Pharmacology

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