High plasma levels of the soluble receptor for advanced glycation endproducts in patients with symptomatic carotid atherosclerosis

Background  Advanced glycation endproducts (AGEs), particularly carboxymethyl(lysine)-adducts (CML), exert part of their cellular effects by binding to a receptor, named receptor for AGEs (RAGE). The soluble form of this receptor (sRAGE) has been shown to have an athero-protective role. We hypothesized the existence of a relationship between the AGE–RAGE axis and the occurrence of symptoms related to carotid atherosclerosis in nondiabetic conditions. Materials and methods  We evaluated plasma levels of CML and sRAGE (by ELISA), and tissue levels (tAGEs and tRAGE, semiquantitatively, by immunohistochemistry) in endarterectomy carotid plaque tissue in 29 nondiabetic patients. At the time of surgery, 10 patients were asymptomatic and 19 were symptomatic. Results  Plasma levels of sRAGE were higher in symptomatic patients than in asymptomatic patients [median (interquartile range): 676 (394–858) pg mL−1 vs. 347 (284–479) pg mL−1, P = 0·009]. In symptomatic patients, plasma levels of sRAGE correlated positively with CML (r = 0·60, P < 0·01), C-reactive protein (CRP) (r = 0·618, P < 0·01) and fibrinogen (r = 0·522, P<0·005), while in asymptomatic patients, no correlation was observed. Although tissue and plasma levels of AGEs and RAGE did not correlate between each other, tAGEs and tRAGE were also positively correlated only in symptomatic patients (χ2 = 8·93, P = 0·003). Conclusions  Plasma levels of sRAGE are higher in symptomatic than asymptomatic carotid atherosclerosis. Higher levels of sRAGE in symptomatic patients may be markers of a higher degree of vascular inflammation in such patients.