Abstract 9844: Endothelial Function is Impaired in Subjects With Increased Ratio of Serum Levels of AGEs to Soluble Form of RAGE

Abstract

Introduction: Advanced glycation end products (AGEs) and their specific receptor, the receptor for AGEs (RAGE), play an important role in atherosclerosis. Recently, a soluble form of RAGE (sRAGE) has been identified in human serum. However, the role of sRAGE in cardiovascular disease is still controversial. There is no information on the association between simultaneous measurements of AGEs and sRAGE and vascular function. In this study, we evaluated the associations between serum levels of AGEs and sRAGE, ratio of AGEs to sRAGE and vascular function. Methods: We measured serum levels of AGEs and sRAGE and assessed vascular function by measurement of flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation in 110 subjects who underwent health examinations. Multivariate regression analyses were performed to identify factors associated with vascular function. Results: Univariate regression analysis revealed that FMD correlated with age (ρ=-0.38, P<0.01), body mass index (ρ=-0.28, P<0.01), systolic blood pressure (ρ=-0.44, P<0.01), diastolic blood pressure (ρ=-0.46, P<0.01), heart rate (ρ=-0.29, P<0.01), triglycerides (ρ=-0.37, P<0.01), high-density lipoprotein cholesterol (ρ=0.19, P<0.05), glucose (ρ=-0.20, P<0.05), smoking pack-years (ρ=-0.32, P<0.01), nitroglycerine-induced vasodilation (ρ=0.40, P<0.01), serum levels of AGEs (ρ=-0.34, P<0.01) and sRAGE (ρ=0.20, P<0.05), and ratio of AGEs to sRAGE (ρ=-0.38, P<0.01). Multivariate analysis revealed that the ratio of AGEs to sRAGE remained an independent predictor of FMD (β=-0.22, P=0.03), while serum level of AGEs alone (β=-0.14, P=0.13) or sRAGE alone (β=0.13, P=0.15) was not associated with FMD. Conclusions: These findings suggest that sRAGE may have a counter-regulatory mechanism that is activated to counteract the vasotoxic effect of the AGEs-RAGE axis. The ratio of AGEs to sRAGE may be a new chemical biomarker of endothelial function.