Angiogenesis induced by advanced glycation end products and its prevention by cerivastatin

SPECIFIC AIMSWe investigated whether advanced glycation end products (AGE), which are senescent macroproteins that form at an accelerated rate in diabetes, elicit changes in cultured endothelial cells (EC) associated with angiogenesis. Angiogenesis is an important characteristic of the vascular derangements in diabetic retinopathy; therefore, we further examined whether cerivastatin, a hydroxymethylglutaryl CoA reductase inhibitor, could prevent AGE-induced angiogenesis by blocking the intracellular signaling pathways of AGE in human microvascular EC.PRINCIPAL FINDINGS1. AGE increased DNA synthesis and tube formation in microvascular EC through interaction with a receptor for AGE (RAGE)We prepared various AGE proteins in vitro by incubating bovine serum albumin (BSA) with D-glyceraldehyde, glycolaldehyde, methylglyoxal, or glyoxal. Of the various AGE proteins, glyceraldehyde- and glycolaldehyde-derived AGE (glycer- and glycol-AGE) were found to significantly stimulate DNA synthesis as well as tube formati...