Expression of receptors for advanced glycation end products in peripheral occlusive vascular disease.

The cellular interactions of advanced glycation end products (AGEs), which have been hypothesized to contribute to the development of vascular lesions, occur, at least in part, through their binding to a novel integral membrane protein, the receptor for AGEs (RAGE). Studies of human vascular segments show that endothelial RAGE expression at the antigen and mRNA level was variable and usually at low levels in samples from healthy individuals. In contrast, patients with a range of peripheral occlusive vascular diseases, with or without underlying diabetes, demonstrated prominent enhancement of endothelial RAGE expression. Smooth muscle cells and nerves in the vessel wall showed constitutively high levels of RAGE expression that were unchanged with aging (from 1 to 92 years) or by the presence of vascular disease. These data suggest that RAGE is likely to have ligands other than AGEs, and that multiple factors in addition to AGEs impact on its expression. Taken together, our findings suggest that RAGE may contribute to the pathogenesis of a range of vascular disorders.

Expression of receptors for advanced glycosylated end-products in renal disease.

BACKGROUND: Advanced glycation endproducts (AGEs) are believed to mediate long-term complications in diabetes mellitus. In this context we studied the expression of the receptor for AGEs (RAGE) in the kidney of patients with a variety of different renal diseases. METHODS: RAGE was detected by immunocytochemistry in renal biopsies. We compared the staining for RAGE in nine patients with diabetic nephropathy, 20 with inflammatory and/or immune complex and 10 with non-inflammatory renal diseases. Normal renal tissue from seven patients with tumour nephrectomies served as controls. RESULTS: In controls the only cells expressing RAGE constitutively were interstitial cells and vascular smooth muscle cells (6/7), while distal tubular cells were rarely positive (1/7). Endothelial cells of arteries/arterioles, glomerular endothelial cells, podocytes, and capsular epithelial cells were consistently negative. In diabetic nephropathy, inflammatory and/or immune complex, and non-inflammatory renal diseases, all cell types mentioned above became positive for RAGE. Whilst the distribution of RAGE in the tissue was quite similar, staining intensity in inflammatory and/or immune complex diseases was higher than in diabetic nephropathy. CONCLUSION: RAGE induction in the kidney is not specific for diabetic nephropathy and occurs in other types of renal diseases as well.