Elevation of soluble form of receptor for advanced glycation end products (sRAGE) in diabetic subjects with coronary artery disease

Kazuo Nakamura, Sho-ichi Yamagishi, Hisashi Adachi, Yayoi Kurita-Nakamura, Takanori Matsui, Takafumi Yoshida, Akira Sato, Tsutomu Imaizumi
Diabetes/metabolism Research and Reviews 2007, 23 (5): 368-71

BACKGROUND: Advanced glycation end products (AGEs)-receptor (RAGE) axis is implicated in diabetic vascular complication. Since a soluble form of RAGE (sRAGE) could be generated from the cleavage of cell surface RAGE in endothelial cells (ECs), serum sRAGE levels may be elevated in diabetes consequent to EC damage. In this study, we examined whether sRAGE levels were elevated in type 2 diabetic patients compared with non-diabetic healthy subjects.

METHODS: Serum sRAGE levels were examined in 75 Japanese type 2 diabetic patients (29 men and 46 women; mean age 66 +/- 11 years) and 75 age- and sex-matched non-diabetic healthy control subjects. We explored the association between sRAGE levels and coronary artery disease (CAD) in diabetic patients.

RESULTS: Serum sRAGE levels were significantly higher in diabetic patients than in non-diabetic subjects (965.3 +/- 544.2 vs 415 +/- 150.4 pg/mL, p < 0.001). In the univariate analysis, diastolic blood pressure (inversely), LDL cholesterol, triglycerides, HDL cholesterol, hemoglobin A(1c), and creatinine were significantly associated with sRAGE. After performing multivariate analyses, the presence of diabetes (p < 0.0001) was a sole independent determinant of sRAGE. Furthermore, there was a significant difference in sRAGE levels between diabetic patients with CAD and those without CAD (1680.6 +/- 891.1 vs 855.2 +/- 372.1 pg/mL, p < 0.001). Multiple stepwise regression analysis revealed that sRAGE and creatinine levels were independent determinants of CAD.

CONCLUSIONS: The present study demonstrated that serum sRAGE levels were significantly higher in type 2 diabetic patients than in non-diabetic subjects and positively associated with the presence of CAD.

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