Lipoprotein Modification by Advanced Glycosylation Endproducts (AGEs): Role in Atherosclerosis

Recent progress in our understanding of advanced glycosylation reactions in vivo has affirmed the hypothesis that these products play an important role in the evolution of both diabetic and nondiabetic vascular disease. Utilizing newly developed advanced glycosylation end-products (AGE)-specific enzyme-linked immunosorbent assay (ELISA) techniques, AGEs have been identified to be present on a variety of vascular wall, lipoprotein, and lipid constituents. Vascular wall AGEs contribute to vascular pathology by increasing vascular permeability, enhancing subintimal protein and lipoprotein deposition, and inactivating nitric oxide. Lipid-linked AGEs present in low-density lipoprotein (LDL) also have been shown to initiate oxidative modification, promoting oxidation reactions that may proceed without the involvement of free metals or other radical generating systems. AGE-specific ELISA analysis has demonstrated a significantly increased level of AGE-modified LDL in the plasma of diabetic patients when compared to normal controls. AGE-modification impairs LDL-receptor-mediated clearance mechanisms in vivo and may contribute to elevated LDL levels in patients with diabetes. This concept has been substantiated further by the recent clinical observations that administration of the advanced glycosylation inhibitor aminoguanidine to diabetic patients significantly decreases circulating LDL levels. (Trends Cardiovasc Med 1997;7:39-47). © 1997, Elsevier Science Inc.