Decreased plasma levels of soluble receptor for advanced glycation end-products in patients with essential hypertension

OBJECTIVES: Advanced glycation end-products (AGE) may cause vascular stiffening by forming crosslinks through the collagen molecule or by interaction with their cellular transductional receptor (RAGE). A secreted isoform of RAGE, termed soluble RAGE (sRAGE), may contribute to the removal/detoxification of AGE by acting as a decoy. Here we studied the plasma sRAGE levels in hypertensive and normotensive human subjects. We also investigated the relationship between blood pressure parameters and plasma sRAGE concentrations. DESIGN: A cross-sectional case-control study. SETTING AND PARTICIPANTS: The outpatient clinic of a university teaching hospital. Participants were 147 never-treated patients with essential hypertension (87 men and 60 women, aged 50 +/- 10 years) and 177 normotensive controls (118 men and 59 women, aged 49 +/- 10 years). MAIN OUTCOME MEASURES: Plasma sRAGE levels determined by enzyme-linked immunosorbent assay, systolic blood pressure (SBP), diastolic blood pressure, pulse pressure (PP) and mean arterial pressure. RESULTS: The plasma concentration of sRAGE [median (interquartile range)] was 1206 (879-1658) pg/ml in hypertensive subjects and 1359 (999-2198) pg/ml in normotensive controls (P = 0.002). Simple correlation analysis revealed that log-transformed sRAGE levels were inversely correlated with SBP (r = -0.11; P < 0.001) and PP (r = -0.23; P < 0.001). Forward-selection multiple regression analysis revealed that log-transformed sRAGE levels were determined more strongly by PP (F = 3.127, P < 0.001). CONCLUSIONS: Plasma sRAGE levels are decreased in patients with essential hypertension and are inversely related to PP. Our results raise the possibility that sRAGE may play a role in arterial stiffening and its complications.