SURVEY OF THE DISTRIBUTION OF A NEWLY CHARACTERIZED RECEPTOR FOR ADVANCED GLYCATION END-PRODUCTS IN TISSUES

Advanced glycation end products (AGEs), the final products of nonenzym atic glycation and oxidation of proteins, are found in the plasma and accumulate in the tissues during aging and at an accelerated rate in d iabetes. A novel integral membrane protein, termed receptor for AGE (R AGE), forms a central part of the cell surface binding site for AGEs. Using monospecific, polyclonal antibody raised to human recombinant an d bovine RAGE, immunostaining of bovine tissues showed RAGE in the vas culature, endothelium, and smooth muscle cells and in mononuclear cell s in the tissues. Consistent with these data, RAGE antigen and mRNA we re identified in cultured bovine endothelium, vascular smooth muscle, and monocyte-derived macrophages. RAGE antigen was also visualized in bovine cardiac myocytes as well as in cultures of neonatal rat cardiac myocytes and in neural tissue where motor neurons, peripheral nerves, and a population of cortical neurons were positive. In situ hybridiza tion confirmed the presence of RAGE mRNA in the tissues, and studies w ith rat PC12 pheochromocytes indicated that they provide a neuronal-re lated cell culture model for examining RAGE expression. Pathological s tudies of human atherosclerotic plaques showed infiltration of RAGE-ex pressing cells in the expanded intima. These results indicate that RAG E is present in multiple tissues and suggest the potential relevance o f AGE-RAGE interactions for modulating properties of the vasculature a s well as neural and cardiac function, prominent areas of involvement in diabetes and in the normal aging process.