OBJECTIVE: Accumulation of advanced glycation end-products (AGE) has been suggested to be involved in several pathophysiological processes in the vessel wall. Soluble isoform of receptor for AGE (sRAGE) acts as a decoy for capturing circulating AGE, thus preventing them from binding to the cell-surface receptor (RAGE) and protecting against the RAGE-AGE axis-elicited processes. We hypothesized that low sRAGE levels might be associated with increased arterial stiffness. DESIGN AND METHOD: In a cross-sectional design, we analyzed 1077 subjects, aged 25 to 64 years, from the Czech population-based study ("Post-MONICA"). Aortic pulse wave velocity (aPWV) measured by the Sphygmocor device, was used to assess aortic stiffness. sRAGE concentrations were assessed in frozen samples by ELISA methods (R&D Systems). RESULTS: Aortic PWV significantly (p < 0.0001) decreased across the sRAGE quartiles. After adjustment for all potential confounders, non-diabetic subjects in the bottom quartile of sRAGE (< 918 pg/mL) had odds ratio of raised aortic PWV (≥ 9.3 m/sec, top quartile) 1.8 (95% CI: 1.19-2.72, p = 0.006); the association was stronger when only hypertensive non-diabetic individuals were included: their odds ratio was 2.05 (95%CI: 1.26-3.32, p = 0.004). In contrast, using similar regression models, low sRAGE was rejected as an independent predictor of raised aortic aPWV in diabetic or in normotensive subjects. CONCLUSIONS: Low circulating sRAGE was independently associated with increased arterial stiffness in a general population-based sample, but mainly in hypertensive non-diabetic patients. The lack of association in diabetics was probably due to low dispersion of sRAGE values and relatively small number of subjects (9% of the sample).

Department of Internal Medicine Biomedical Centre Charles University Medical Faculty Czech Republic

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