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

Abstract

IntroductionAdvanced glycation end products (AGEs) are produced and can accumulate during chronic inflammation, as might be present in patients with rheumatoid arthritis (RA). AGEs are involved in the development of cardiovascular disease. The aim of this study is to evaluate whether AGEs are increased in patients with long-standing RA and whether AGE accumulation is related to disease activity, disease severity and measures of (premature) atherosclerosis, such as endothelial activation, endothelial dysfunction and intima media thickness (IMT).MethodsIn a cross-sectional study, 49 consecutive RA patients with longstanding disease (median disease duration of 12.3 years (range 9.3 to 15.1)), receiving standard of care, were included and compared with 49 age- and sex-matched healthy controls (HC). AGEs were determined by skin autofluorescence. Disease activity was evaluated by the Disease Activity Score of 28 joints (DAS-28) score and joint damage by modified Sharp-v.d. Heijde score. Endothelial activation (soluble vascular cellular adhesion molecule-1) sVCAM-1, von Willebrand factor (vWF), thrombomodulin), endothelial dysfunction (determined by small artery elasticity (SAE)) and IMT were measured and related to AGE accumulation.ResultsAGEs were increased in RA patients (median 2.4 arbitrary units (a.u.), range 1.6 to 4.2) compared to HC (2.2, 1.3 to 3.8). RA patients had a DAS-28 score of 2.9 (0.8 to 6.9) and a modified Sharp-v.d. Heijde score of 19 (0 to 103). sVCAM-1 and vWF levels were higher in RA patients. SAE was significantly decreased in RA (3.9 ml/mmHg (1.4 to 12.2) vs. 6.1 in HC (1.7 to 12.9). IMT did not differ between the two groups. Combining both groups' AGEs correlated with vWF, sVCAM-1 and IMT, and was inversely related to SAE. In RA, AGEs had an inverse relation with SAE, but did not relate to disease activity or radiological damage. In multivariate analysis for both groups, smoking, glucose levels, vWF, SAE and male gender were significantly related to the formation of AGEs.ConclusionsAGEs were increased in RA patients with long-standing disease and without signs of premature atherosclerosis. AGEs were related to endothelial activation and endothelial dysfunction. This supports the hypothesis that in RA AGEs may be an early marker of cardiovascular disease.

Intake of high fructose corn syrup sweetened soft drinks, fruit drinks and apple juice is associated with prevalent coronary heart disease, in U.S. adults, ages 45–59 y

“…In 2003-2006 [the NHANES study period], high fructose corn syrup was the main sweetener in US soft drinks [31]. Odds ratios were considered statistically significant if the 95% confidence intervals did not include 1 and p values were <0.05, as indicated by italics accumulate in the pancreas and contribute to pancreatitis and impaired ß-cell function; [58,59] AGE are elevated in connective tissues including the synovium, sub-lining, and cartilage of autoimmune arthritis sufferers [71][72][73][74][75]; and the receptor of advanced glycation end-products (RAGE) is a key mediator of asthma [76].…”

Glycoxidation of histone proteins in autoimmune disorders

“…It has been proposed that prolonged exposure to oxidative stress and AGE accumulation leads to endothelial activation, small artery elasticity and intima media thickness (IMT), and to markers of disease damage. RAGE (receptor for advanced glycation end products) over expression by cytokines such as IL-1 has been reported to amplify the inflammatory responses mediated by RAGE ligands that are abundant in RA joints [73,74]. Oxidation of histone H2A proteins has been correlated with the pathogenesis of RA by stimulating T and B lymphocytes, especially T helper (Th)1 cells.…”

Depression and Smoking Augment the Production of Circulating Autoantibodies against Glycated HSA in Rheumatoid Arthritis Patients

“…AGEs are produced and might accumulate in patients with RA. An increase in this accumulation has been observed, associated in particular to smoking, male sex, glucose levels, endothelial activation, and endothelial dysfunction [12]. In RA, AGEs can be generated as a result of oxidative stress during inflammation.…”

“…These tend to accumulate and are found in patients with RA [12][13][14]. Antibodies against glucose-modified immunoglobulin (Ig)G and AGEs such as pentosidine have been discovered in the serum as well as in the synovial fluid of RA [15,16].…”