GLYCATED ALBUMIN MODIFIED BY AMADORI ADDUCTS MODULATES AORTIC ENDOTHELIAL-CELL BIOLOGY

Increased protein glycation has been mechanistically linked to acceler ated vascular pathobiology in diabetes. To test the influence of prote in modified by Amadori glucose adducts on vascular cell biology, we ex amined the effect of glycated albumin on replicative capacity and base ment membrane collagen production by aortic endothelial cells in cultu re. Relative to carbohydrate-free albumin, which supported cell prolif eration and Type IV collagen synthesis, glycated albumin significantly inhibited H-3-thymidine incorporation and Type IV collagen production . The glycated albumin-induced effects were prevented by monoclonal an tibodies (A717) that specifically react with Amadori-modified albumin, but not by IgG that was unreactive with glycated albumin. A717 had no effect on thymidine incorporation or collagen synthesis by cells cult ured in the presence of nonglycated albumin. The findings indicate tha t the interaction of glycated albumin with endothelial cells, which ha ve been shown to display dose-responsive, saturable receptors, limits cell replication and triggers maladaptive biosynthetic programs, which may contribute to degenerative macrovascular disease in diabetes.