Role of nonenzymatic glycosylation in atherogenesis.
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 increase 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.
D001161:Arteriosclerosis / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D007093:Imidazoles / Q000032:analysis; D008077:Lipoproteins, LDL / Q000378:metabolism; D008954:Models, Biological; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D013997:Time Factors
D001786:Blood Glucose; D007093:Imidazoles; D008077:Lipoproteins, LDL; D010982:Platelet-Derived Growth Factor; D011506:Proteins; D004247:DNA; C041306:2-(2-furoyl)-4(5)-(2-furanyl)-1H-imidazole; D002784:Cholesterol; D005947:Glucose