Advanced Glycation End Products

Abstract

Abstract-Advanced glycation end products (AGEs) are proteins or lipids that become glycated after exposure to sugars.AGEs are prevalent in the diabetic vasculature and contribute to the development of atherosclerosis. The presence and accumulation of AGEs in many different cell types affect extracellular and intracellular structure and function. AGEs contribute to a variety of microvascular and macrovascular complications through the formation of cross-links between molecules in the basement membrane of the extracellular matrix and by engaging the receptor for advanced glycation end products (RAGE). Activation of RAGE by AGEs causes upregulation of the transcription factor nuclear factor-B and its target genes. Soluble AGEs activate monocytes, and AGEs in the basement membrane inhibit monocyte migration. AGE-bound RAGE increases endothelial permeability to macromolecules. AGEs block nitric oxide activity in the endothelium and cause the production of reactive oxygen species.

Combined effects of physiologically relevant disturbed wall shear stress and glycated albumin on endothelial cell functions associated with inflammation, thrombosis and cytoskeletal dynamics

“…Our data suggest an additive increase in the expression of ICAM‐1 after exposure to irreversibly glycated albumin and pathological shear stress, which is in agreement with our previous findings14. Previously, it has been reported that AGEs can mediate an enhancement of ICAM‐1 expression both in vivo and in vitro 4. Furthermore, ICAM‐1 expression has been shown to be sensitive to shear stress in vitro 9, and in vivo ICAM‐1 expression is most pronounced at locations of disturbed wall shear stress20.…”

“…AGEs are heterogeneous compounds that alter cellular effects through the receptor for advanced glycation end‐products (RAGE). AGE–RAGE interactions induce the generation of reactive oxygen species and the activation of nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB)4. This leads to the enhanced expression of adhesion molecules (inter‐cellular adhesion molecule [ICAM‐1], vascular cell adhesion molecule [VCAM‐1]) and pro‐inflammatory cytokines (interleukin‐1, interleukin‐6).…”

“…It has been reported that elevated, low mean oscillatory and recirculation shear upregulate pro‐inflammatory and pro‐thrombotic markers11, along with disrupting cytoskeletal organization. Interestingly, the presence of AGEs exerts similar effects through NF‐κB activation4. Additionally, a disruption in the connexin‐43 network has been shown to be associated with EC dysfunction under diabetic conditions12.…”

Diabetes and shoulder disorders

“…In fact, hyperglycemia is linked to subsequent formation of non‐enzymatic glycosylation products, and further gives rise to advanced glycosylation end‐products (AGEs). These AGEs increase cross‐linking in collagen, tendons and ligaments, making these structures stiffer and weaker4. In addition, AGEs interact with their receptors on the surface of tenocytes and fibroblasts, thereby inducing inflammatory changes4.…”

Diabetic nephropathy: newer therapeutic perspectives

“…These receptors initiate maladaptive changes by initiating certain intracellular pathways, which disrupt cellular function. Advanced glycation end products-receptors for advanced glycation end products (AGE-RAGE) axis is now recognized to be an important pathway through which diabetes contributes to vascular damage [58]. …”