Survey of the distribution of a newly characterized receptor for advanced glycation end products in tissues

Abstract

Advanced glycation end products (AGEs), the final products of nonenzymatic glycation and oxidation of proteins, are found in the plasma and accumulate in the tissues during aging and at an accelerated rate in diabetes. A novel integral membrane protein, termed receptor for AGE (RAGE), forms a central part of the cell surface binding site for AGEs. Using monospecific, polyclonal antibody raised to human recombinant and bovine RAGE, immunostaining of bovine tissues showed RAGE in the vasculature, endothelium, and smooth muscle cells and in mononuclear cells in the tissues. Consistent with these data, RAGE antigen and mRNA were 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 hybridization confirmed the presence of RAGE mRNA in the tissues, and studies with rat PC12 pheochromocytes indicated that they provide a neuronal-related cell culture model for examining RAGE expression. Pathological studies of human atherosclerotic plaques showed infiltration of RAGE-expressing cells in the expanded intima. These results indicate that RAGE is present in multiple tissues and suggest the potential relevance of AGE-RAGE interactions for modulating properties of the vasculature as well as neural and cardiac function, prominent areas of involvement in diabetes and in the normal aging process.