Irbesartan inhibits advanced glycation end product (AGE)-induced up-regulation of vascular cell adhesion molecule-1 (VCAM-1) mRNA levels in glomerular endothelial cells.

Renin-angiotensin system (RAS) plays a central role in the development and progression of diabetic nephropathy. There is a growing body of evidence that advanced glycation end products (AGE) and inflammation contribute to diabetic nephropathy as well. However, the pathophysiological crosstalk between the RAS and AGE in inflammatory reactions in glomerular endothelial cells (ECs) remains unknown. In this study, we examined whether and how irbesartan, an angiotensin II type 1 receptor blocker (ARB), inhibited the AGE-induced vascular cell adhesion molecule-1 (VCAM-1) gene expression in cultured human glomerular ECs. Irbesartan or an anti-oxidant N-acetylcysteine inhibited the AGE-induced increase in reactive oxygen species (ROS) generation and subsequently blocked up-regulation of VCAM-1 mRNA levels in glomerular ECs. AGE significantly stimulated angiotensin II production by glomerular ECs. Furthermore, irbesartan completely suppressed up-regulation of VCAM-1 mRNA levels in AGE plus angiotensin II-exposed glomerular ECs. Our present data suggest that there exists a crosstalk between the RAS and AGE in inflammatory reactions in glomerular ECs. Irbesartan may play a protective role against diabetic nephropathy by blocking the deleterious effects of AGE-elicited angiotensin II and ROS.