Nonenzymatic glycosylation products on collagen covalently trap low-density lipoprotein

Advanced nonenzymatic glycosylation products capable of cross-linking proteins accumulate on collagen in vivo in proportion to time-averaged blood glucose concentration. In this report, we have evaluated the ability of advanced nonenzymatic glycosylation products formed on collagen in vitro to covalently bind low-density lipoprotein (LDL) in a manner similar to that which occurs in human atherosclerotic lesions. At constant LDL concentration, covalent trapping increased linearly with the extent of advanced glycosylation product formation, from 1.42 ± 0.15 to 4.46 ± 0.36 μg LDL protein/mg collagen. At a constant level of collagen advanced glycosylation product LDL binding increared as a function of increasing LDL concentration. At an LDL-cholesterol level of 103 mg/dl, covalent trapping of LDL by nonenzymatic glycosylation products on collagen averaged 3.2 times as much as control (P < 0.01). These data indicate that LDL is bound specifically by reactive products generated by nonenzymatic glycosylation of collagen, and suggest that excessive LDL trapping by hyperglycemia-induced advanced glycosylation endproducts may contribute to the accelerated development of atherosclerosis in patients with diabetes mellitus.