Modulation of Nitric Oxide Pathway by Multiligands/RAGE Axis: A Crossing Point on the Road to Microvascular Complication in Diabetes

The formation of advanced glycation end-products (AGEs), also called the Maillard reaction, occurs ubiquitously and irreversibly in patients with diabetes mellitus and its consequences are especially relevant to many inflammatory events leading to vascular dysfunctions and organ injury. The present review intends to highlight some relevant aspects of nitric oxide synthases, advanced glycation end-products and their receptors as well as the mechanisms by which AGEs are able to modulate the synthesis of nitric oxide (NO), either by NO quenching, modification of enzyme structure or regulation of gene expression. Finally, other RAGE ligands different from AGEs, but relevant to the context of inflammation, are presented as new modulators of nitric oxide synthesis.