Circulating levels of soluble receptor for advanced glycation end product are inversely associated with vascular calcification in patients on haemodialysis independent of S100A12 (EN-RAGE) levels

Abstract

AimThe receptor for advanced glycation end products (RAGE) has emerged as a central regulator of vascular inflammation and atherosclerosis. Soluble RAGE (sRAGE) has an anti-inflammatory effect by quenching ligands for RAGE. On the other hand, extracellular RAGE-binding protein S100A12 (EN-RAGE) shows a pro-inflammatory effect in a way, but may play pleiotropic roles related to inflammatory process. Therefore, we determined the levels of sRAGE and S100A12 in haemodialysis (HD) patients and evaluated their relationship with vascular calcification. MethodsWe performed a cross-sectional study with 199 HD patients. Plain X-ray images of the lateral lumbar spine from all subjects were studied to calculate semiquantitative vascular calcification scores (VCS), as described by Kauppila. Commercially available enzyme linked immunosorbent assay (ELISA) kits were used to quantify the serum concentration of sRAGE and S100A12. ResultsThe patients were 57.113.7 years of age; 54.3% were male, 49.2% were diabetic, and 36.2% had a history of cardiovascular disease. In a univariate analysis, serum sRAGE was negatively associated with VCS (log sRAGE, r=-0.208, P=0.003), whereas S100A12 showed a positive tendency (log S100A12, r=0.235, P=0.085). Even after adjustments for confounding risk factors, sRAGE was independently associated with VCS (=-1.679, P=0.002). ConclusionThis study demonstrated that the circulating sRAGE level was inversely associated with VCS in HD patients independent of the S100A12 level and the severity of systemic inflammation. Summary at a Glance Soluble RAGE (sRAGE) has anti-inflammatory effects by counteracting the receptor for advanced glycation end products (RAGE), a central regulator of vascular inflammation and atherosclerosis. This study reports an inverse association between sRAGE and vascular calcification in haemodialysis patients, independent of the extracellular RAGE-binding protein S100A12 (EN-RAGE) which is pro-inflammatory and may have a pleiotropic role in inflammatory processes.