Association between endogenous secretory RAGE, inflammatory markers and arterial stiffness

Background: Advanced glycation end products (AGEs) and its receptor (RAGE) were known to play a pivotal role in the development of cardiovascular complications of diabetes. We investigated the association between circulating endogenous secretory RAGE (esRAGE) levels, inflammatory markers and arterial stiffness measured using brachial-ankle pulse wave velocity (baPWV). Methods: The study subjects were composed of 76 type 2 diabetic patients and 78 age- and sex-matched non-diabetic subjects. Results: Circulating esRAGE levels were significantly lower in subjects with type 2 diabetes (0.237 ± 0.123 ng/ml vs. 0.307 ± 0.177 ng/ml, p = 0.005), and those levels were inversely correlated with body mass index (BMI), waist circumference, blood pressure, triglyceride, fasting glucose level and insulin resistance. Furthermore, esRAGE levels were significantly associated with adiponectin (r = 0.164, p = 0.044), interleukin-6 (IL-6) (r = - 0.242, p = 0.009) levels and baPWV (r = - 0.296, p < 0.001). Multiple regression analysis showed that fasting insulin, IL-6, glucose level and insulin resistance are major factor determining esRAGE (R² = 0.186). Moreover, baPWV was found to be associated with age, systolic blood pressure, triglyceride, sex, BMI, fasting insulin and esRAGE level (R² = 0.583). Conclusions: Circulating esRAGE levels were significantly lower in type 2 diabetic patients, and were associated with inflammation and arterial stiffness. These results suggest that esRAGE may play an important role on ligand-RAGE interaction propagated inflammation and atherosclerosis.