Impact of Advanced Glycation End Products on Endothelial Function and Their Potential Link to Atherosclerosis

Abstract

The role of advanced glycation end products (AGEs) in cardiovascular diseases is a matter of interest in the last years and the strong association between the action of AGEs on their receptor (RAGE) and atherosclerosis has attracted increased attention. The aim of this chapter is to review the results of our laboratory and others on the molecular mechanisms triggered by AGEs in the endothelium that could participate in the atherosclerotic process. These mechanisms and molecular pathways could be the source of new therapeutic targets against atherosclerosis or vascular disease. Oxidative stress in endothelium induced by AGEs triggers molecular signaling pathways that produce an inflammatory response or even endothelial dysfunction. Adhesion molecules expression at the membranes of endothelial cells as a consequence of this response or induced by other mechanisms involving AGEs mediates the adhesion of leukocytes to endothelium. This adhesion is a key step in the atherogenesis process and the possible involvement of AGE-RAGE axis in this process should be considered as a potential therapeutic target. Finally, potential pharmacological modulation of AGE-RAGE axis activity at the endothelium is suggested, but the specific pharmacological tools available nowadays are missing; respectively, drugs used for the treatment of cardiovascular and metabolic diseases could be helpful for AGE-RAGE axis modulation, thus also affecting endothelial (dys)function.

Determinants of self-reported hypertension among women in South Africa: evidence from the population-based survey

“…Thus, the renin–angiotensin–aldosterone system may be upregulated in diabetes, resulting in increased blood pressure through a direct effect mediated by angiotensin II [ 106 ], as well as indirectly through upregulation of sympathetic activity [ 107 ]. Another essential connection between HTN and diabetes is the occurrence as well as the progression of diabetic kidney disease [ 108 ], the pathophysiology of which is mediated through several pathways including endothelial dysfunction and advanced glycation end-products [ 109 ]. Furthermore, obesity and metabolic syndrome, through their effects on various hormones and inflammation pathways, may also influence the occurrence of HTN and diabetes [ 107 ].…”

Relationship between vascular cell adhesion molecule-1 (VCAM-1), soluble receptor for advanced glycation end products (sRAGE) and functional hemodynamic parameters of arteriovenous fistula

“…30 Experimentally, blockage of RAGE using soluble forms of RAGE or anti RAGE antibody decreased atherosclerotic lesion and VCAM-1 level. 31 In contrast, Alvarez et al 32 showed that blockage of RAGE was not sufficient to counteract the AGE-induced VCAM-1 expression, which may suggest that other RAGE independent mechanisms may be acting to increase adhesion molecule. As mentioned, neointimal proliferation is an essential process in AVF failure.…”

How do Uremic Toxins Affect the Endothelium?

“…Their accumulation in CKD promotes endothelial dysfunction and subsequent diseases [ 115 , 116 , 117 , 118 , 119 , 120 ]. Atherosclerosis, autoimmune disease, diabetes mellitus, and inflammatory diseases are closely linked to the AGE receptor-ligand axis [ 121 , 122 , 123 , 124 ]. AGEs induce cell injury by interacting with their receptor, denominated receptor for advanced glycation end products (RAGE), which is a ubiquitous multiligand transmembrane cell surface receptor of the immunoglobulin superfamily [ 116 , 125 , 126 , 127 ].…”