Advanced glycation end products, oxidant stress and vascular lesions

Abstract

The formation of advanced glycation end products (AGEs) is observed in conditions such as diabetes mellitus and ageing, both associated with vascular disorders. AGEs form by the interaction of an aldose with NH2 of proteins, and the subsequent Amadori rearrangement leads to complex molecules. The heterogeneous class of AGE molecules is found in plasma, cells and tissues and accumulates in the vessel wall and the kidney. AGE reactions can generate reactive oxygen intermediates (ROIs), which can act as signal mediators and can be deleterious for molecules or cells. The AGEs and ROI-induced cellular dysfunctions can interfere with the gene expression of peptides and cytokines regulating cell proliferation and vascular functions. The interaction of AGEs with the AGE receptor (RAGE) is followed by a series of intracellular modifications that may be involved in the development of atherosclerosis. An attempt to minimize AGE formation and to limit ROI production by an appropriate therapy may result in the reduction or slowing of vascular disease in patients with diabetes mellitus.

Receptor for AGE (RAGE) Mediates Neointimal Formation in Response to Arterial Injury

“…16 AGEs are increased at sites of atherosclerotic lesions, especially in diabetes. 17,18 Increased expression of AGEs have also been found in settings like renal failure and amyloidosis, indicating the biology of AGEs extends beyond diabetes. The cellular effects of AGEs are largely mediated by their specific engagement of cell surface receptor RAGE.…”

The Potential Effect of Some Newer Risk Factors for Atherosclerosis on Aortic Distensibility in Subjects With and Without Type 2 Diabetes

“…Long duration of diabetes is associated with a decline in aortic elastin and glycation-induced molecular cross-links, which compromise elasticity of the aorta (9,10).…”

Role of mitochondrial DNA variants and copy number in diabetic atherogenesis

“…A growing body of evidence suggests that oxidative stress plays a key role in the pathogenesis of atherosclerotic cardiovascular disease (Ross, 1993;Puddu et al, 2005;Gutierrez et al, 2006;Madamanchi and Runge, 2007). Hyperglycemia-induced formation of advanced glycation end-products can generate ROS (Chappey et al, 1997); ROS are associated with somatic DNA mutations, which may contribute to atherogenesis (Rosen et al, 2001;Brownlee, 2001). Several genetic polymorphisms may also play a role in the development and progression of atherosclerosis in diabetic patients.…”