Role of nonenzymatic glycosylation in atherogenesis

Anthony Cerami, Helen Vlassara, Michael Brownlee

Research output: Contribution to journalReview article

42 Scopus citations

Abstract

This review summarizes progress in nonenzymatic glycosylation research of potential relevance to atherosclerosis using a hypothetical model based on current concepts of atherogenesis. Recently, new information has been presented showing that the initial Amadori product undergoes a series of further reactions and rearrangements to form adducts, called advanced glycosylation end products (AGE). These products are irreversible and accumulate indefinitely on long‐lived molecules. These AGE covalently trap soluble plasma proteins, act as signals for macrophage recognition and uptake, and induce mutations in double‐stranded plasmid DNA. Covalent trapping of low‐density lipoprotein (LDL) by AGE on collagen or elastin could promote lipid accumulation in the arterial wall, whereas AGE trapping of von Willebrand factor would increse platelet adhesion and aggregation leading to intimal smooth muscle cell proliferation. Recognition and uptake of AGE‐proteins by scavenging macrophages could further contribute to the process of atherogenesis by stimulating release of macrophage secretory products such as macrophage‐derived growth factor. Accumulation of AGE on smooth muscle cell DNA might also enhance arterial smooth muscle cell proliferation by increasing the rate of mutations affecting growth controls. This model should provide the basis for future experiments.

Original languageEnglish (US)
Pages (from-to)111-120
Number of pages10
JournalJournal of Cellular Biochemistry
Volume30
Issue number2
DOIs
Publication statusPublished - 1986

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Keywords

  • 2‐furoyl‐4(5)‐(2‐furanvl)‐1H‐imidazole(FFI)
  • DNA
  • MDGF
  • PDGF
  • advanced glycosylation end products (AGE)
  • cross‐linking of proteins
  • low‐density lipoprotein
  • macrophage recognition
  • von Willebrand factor

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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