Abstract
Advanced glycation endproducts (AGE) are non-enzymatically glycated protein derivatives, which are formed acceleratedly under hyperglycemic conditions. Here we describe effects of AGE on the growth and function of endothelial cells (EC). When human umbilical vein EC are exposed to AGE, DNA synthesis as well as viable cell number is increased, while prostacyclin production is significantly inhibited. This is mainly mediated by the interaction between AGE and a cell surface receptor for AGE (RAGE). AGE also stimulate the growth and tube formation of microvascular EC, the key steps of angiogenesis, through an autocrine induction of vascular endothelial growth factor. Moreover, AGE increase plasminogen activatior inhibitor-1 production by microvascular EC, thus attenuating the fibrinolytic activity. The results indicate that AGE-RAGE interactions may predispose to angiogenesis and thrombogenesis, thereby leading to the development and progression of diabetic angiopathies.
