Rheumatoide Arthritis: Zusammenhänge zwischen kardiovaskulären Erkrankungen und dem "Advanced Glycation End Product Receptor"

Abstract

Cardiovascular (CV) disease is increased in patients with chronic inflammatory disease, including rheumatoid arthritis (RA). Furthermore it has become clear at a pathophysiological level, that atherosclerosis has striking similarities with autoimmune disease. This realization has come at a time of paradigm shift in how rheumatologists manage RA, with the availability of biological agents targeting key inflammatory cytokines. This review will focus on the possible causes of increased vascular disease in RA, including the role of traditional CV risk factors. Mechanisms potentially at play, such as C-reactive protein (CRP), altered coagulation, and cyclooxygenase (COX)-2 inhibitors will be covered in brief. The receptor for advanced glycation end products (RAGE) has been identified as a candidate molecule influencing response to ongoing inflammation and autoimmunity. There will be a focus on the role of RAGE in CV disease and RA. As has been the case with many novel molecules, functional polymorphisms are thought to alter disease expression and assist us in coming to terms with the biological activities of the parent molecule. The review will conclude with a discussion of the potential role of the RAGE Glycine 82 Serine polymorphism.

Advanced glycation endproducts are increased in rheumatoid arthritis patients with controlled disease

“…In the nucleus, NF-κB facilitates the transcription of pro-inflammatory genes, finally resulting in, for example, the up-regulation of sVCAM-1. In this way a positive feed-back loop of AGE-RAGE interaction is established, maintaining an inflammatory status in which AGEs can be formed [17,21,41]. …”

Risk factors and early detection of atherosclerosis in rheumatoid arthritis

“…Under the influence of NF‐κB, pro‐inflammatory genes are activated [18]. This process of AGE‐RAGE interaction can have a positive feedback loop and thus maintain endothelial inflammation [19].…”

Efficacy of glycoprotein enrichment by microscale lectin affinity chromatography

“…For example, the solubility and stability of a protein is dependent on glycosylation [5], while this type of modification directly influences intra- and extracellular trafficking of proteins, as well as mediating and modulating both cell signaling and cell adhesion [6-9]. Moreover, aberrant glycosylation of proteins has been recognized as an attribute of many diseases, including rheumatoid arthritis [10], prion diseases [11], congenital disorders of glycosylation [12], cardiovascular diseases [10], and cancer [5, 13-18]. …”