抄録
The nonenzymatic glycation of body proteins, including extracellular matrix and plasma proteins, is thought to contribute to the development of atherosclerosis. The present study was performed to clarify the mechanism by which the glycated extracellular matrix accelerates the development of atherosclerotic lesions. First, we found the different localization of different epitopes of advanced glycation end products (AGEs) in atherosclerotic lesions. Namely, Nε-(Carboxymethyl) lysine (CML), one of epitopes of AGEs, was localized mainly in macrophages or their related foam cells. In contrast, non-CML, another epitope of AGEs, was accumulated mainly in extracellular matrices and atheroma of intima. Second, when acid-soluble type I collagen was incubated with D-glucose in phosphate buffer, pH 7.4, at 37°C for 8 weeks, AGE-related cross-links were formed between collagen molecules. AGE contents were significanly greater in pepsin-insoluble collagen of rat aorta than pepsin-soluble collagen. In diabetic rats, AGEs were increased in pepsin-insoluble collagen, but not in pepsin-soluble collagen. Third, Glycated bovine serum albumin (BSA) showed a concentration-dependent cytotoxicity in smooth muscle cells in the presence of copper ion, but not in endothelial cells. When the cells were incubated with glycated BSA in the presence of copper ion, the extracellular generation of hydrogen peroxide was significantly less in endothelial cells than in smooth muscle cells. These results suggest that nonenzymatic glycation of extracellular matrix may contribute to the development of atheroslcerotic lesions throught the accumulation of lipid and collagen and smooth muscle cell injury.
