Ratio of serum levels of AGEs to soluble form of RAGE is a predictor of endothelial function

Diabetes Care. 2015 Jan;38(1):119-25. doi: 10.2337/dc14-1435. Epub 2014 Oct 21.


Objective: 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.

Research design and 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, BMI, systolic blood pressure, diastolic blood pressure, heart rate, triglycerides, HDL cholesterol, glucose, smoking pack-years, nitroglycerine-induced vasodilation, serum levels of AGEs and sRAGE, and ratio of AGEs to sRAGE. Multivariate analysis revealed that the ratio of AGEs to sRAGE remained an independent predictor of FMD, while serum level of AGEs alone or sRAGE alone was not associated with FMD.

Conclusions: These findings suggest that sRAGE may have a counterregulatory mechanism that is activated to counteract the vasotoxic effect of the AGE-RAGE axis. The ratio of AGEs to sRAGE may be a new chemical biomarker of endothelial function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Atherosclerosis / blood
  • Biomarkers / blood
  • Blood Glucose / metabolism
  • Blood Pressure
  • Body Mass Index
  • Cardiovascular Diseases / blood
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Cross-Sectional Studies
  • Endothelium, Vascular / physiopathology*
  • Female
  • Glycated Hemoglobin A / metabolism
  • Glycation End Products, Advanced / blood*
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic / blood*
  • Regression Analysis
  • Risk Factors
  • Triglycerides / blood
  • Vasodilation


  • Biomarkers
  • Blood Glucose
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Glycated Hemoglobin A
  • Glycation End Products, Advanced
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic
  • Triglycerides