Low Soluble Receptor for Advanced Glycation End Products Precedes and Predicts Cardiometabolic Events in Women With Rheumatoid Arthritis.

Mitra Nadali,Sofia Töyrä Silfverswärd,Lovisa Lyngfelt,Karin M E Andersson,Malin C Erlandsson,Rille Pullerits,Maria I Bokarewa

doi:10.3389/fmed.2020.594622

Mitra Nadali, Sofia Töyrä Silfverswärd + Show 5 more

Open Access

https://doi.org/10.3389/fmed.2020.594622

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Abstract

Background: Cardiovascular disease (CVD) causes premature mortality in rheumatoid arthritis (RA). Levels of soluble (s)RAGE change with aging, hypertension and hypercholesterolemia. We assessed whether sRAGE was associated with increased risk of CVD in RA patients.Methods: Serum sRAGE was measured in 184 female RA patients and analyzed with respect to CVD risk estimated by the Framingham algorithm (eCVR), metabolic profile and inflammation. Levels of sRAGE in 13 patients with known cardio-metabolic morbidity defined the cut-off for low sRAGE. Prospective 5-year follow-up of new CV and metabolic events was completed.Results: Low sRAGE was significantly associated with previous history and with new imminent cardiometabolic events in the prospective follow-up of RA patients. In both cases, low sRAGE reflected higher estimation of CVR in those patients. Low sRAGE was attributed to adverse metabolic parameters including high fasting plasma glucose and body fat content rather than inflammation. The association of sRAGE and poor metabolic profile was prominent in patients younger than 50 years.Conclusions: This study points at low sRAGE as a marker of metabolic failure developed during chronic inflammation. It highlights the importance for monitoring metabolic health in female RA patients for timely prevention of CVD.Trial registration: ClinicalTrials.gov with ID NCT03449589. Registered 28, February 2018.

Highlights

Glycation is the process of non-enzymatic binding of sugar molecules glucose and fructose with proteins, lipids and nucleic acids
We have previously reported that chronic inflammation in rheumatoid arthritis (RA) is associated with significantly lower serum soluble form of RAGE (sRAGE) compared to healthy controls and patients with non-inflammatory joint diseases [23]
Out of 184 patients included at the baseline, we identified 7 patients with type 2 diabetes (T2D) and 6 patients with previous CV events

Summary

Introduction

Glycation is the process of non-enzymatic binding of sugar molecules glucose and fructose with proteins, lipids and nucleic acids. Glycation directly depends on glucose concentration and occurs at random sites of a molecule. It leads to the loss of molecule’s function and degradation into the advanced glycation end products (AGEs) [1]. Circulating AGEs in the extracellular compartment activate the proinflammatory receptor for advanced glycation end products (RAGE) and participate in perpetuation of inflammation [2]. Other non-glycated RAGE ligands such as S100 proteins and HMGB1 are accumulated. RAGE ligands induce proinflammatory signaling through the membrane-bound RAGE causing nuclear translocation of NFkappa B followed by cytokine production [2]. We assessed whether sRAGE was associated with increased risk of CVD in RA patients

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