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Long-term incubation of proteins with glucose results in formation of advanced glycation end products (AGEs) through early products, such as Shiff base and Amadori rearrangement products. AGEs are characterized by autofluorescence, brown color, and intra-and intermolecular cross-linking. Recent immunochemical and immunohistochemical demonstration of AGEs by anti-AGE antibodies in several human tissues has suggested an important role of AGEs in the aging process, diabetic complications, and atherosclerosis. In the present study, we examined the distribution and subcellular localization of AGEs in various human and bovine tissues by immunohistochemistry and immunoelectron microscopy using a monoclonal antiboby specific for AGEs (6D12). In most tissues of old human and aged bovine, the accumulation of AGEs was found in macrophages, endothelial cells, adventitial cells or pericytes, and parenchymal cells such as hapatocytes or adrenocortical cells. Deposition of AGEs was also found in the extracellular matrix. Immunoelectron microscopy demonstrated the localization of AGEs in the endosomal and lysosomal compartments of various types of cells and in the extracellular matrix. Immunohistochemistry of human atherosclerotic lesions disclosed the deposition of AGEs in various atherosclerotic lesions. Compared with diffuse intimal thickening, intracellular AGE accumulation was marked in the fatty streaks and atheromatous plaques. Extracellular deposition of AGEs was also found in most atherosclerotic lesions. Accumulation of AGEs in the intimal lesions of atherosclerosis was considered to occur in relation to aging and the progression of atherogenesis. Through the observation of intracellular processing of AGEs in bovine macrophages, participation of macrophage scavenger receptors in the endocytotic uptake of AGEs was confirmed.

Advanced Glycation End Products of Maillard Reaction and Aging.