title: Positive association between serum levels of advanced glycation end products and the soluble form of receptor for advanced glycation end products in nondiabetic subjects.
abstract: The advanced glycation end products (AGEs)-receptor for AGE (RAGE) axis is implicated in diabetic vascular complications. Administration of soluble form of RAGE (sRAGE) to mice has been shown to block the AGE-elicited tissue damage by acting as a decoy. These observations suggest that endogenous sRAGE may capture and eliminate circulating AGEs and decrease its serum levels. However, because AGEs up-regulate tissue RAGE expression and endogenous sRAGE could be generated from the cleavage of cell surface RAGE, sRAGE may be positively, rather than inversely, associated with circulating AGEs by reflecting tissue RAGE expression. In this study, we investigated the association of sRAGE with serum levels of AGEs in humans. Data for fasting serum sRAGE and AGE levels of 184 nondiabetic subjects were obtained from a general population in Japan. We also measured body mass index (BMI), waist circumference, blood pressure, and blood biochemistries in this population. Uni- and multivariate analyses were applied for the determinants of serum sRAGE levels. The average sRAGE levels were 0.40 +/- 0.17 ng/mL in males and 0.43 +/- 0.14 ng/mL in females, respectively. In the univariate analysis, BMI (P < .05, inversely), waist circumference (P < .05, inversely), AGEs (P < .05), and alcohol intake (P < .05, inversely) were significantly associated with sRAGE levels. After performing multivariate analyses, BMI (P < .05, inversely) and AGEs (P < .05) still remained significant independently. The present study is the first demonstration that serum sRAGE levels were positively associated with circulating AGEs in the nondiabetic general population. Endogenous sRAGE levels are elevated in parallel with serum AGE levels.
authors.affiliation: The Third Department of Internal Medicine and Cardiovascular Research Institute, Kurume University School of Medicine, Kurume 830-0011, Japan. shoichi@med.kurume-u.ac.jp
authors.forename: Sho-ichi
authors.initials: S
authors.lastname: Yamagishi
authors.forename: Hisashi
authors.initials: H
authors.lastname: Adachi
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nakamura
authors.forename: Takanori
authors.initials: T
authors.lastname: Matsui
authors.forename: Yuko
authors.initials: Y
authors.lastname: Jinnouchi
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Takenaka
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Takeuchi
authors.forename: Mika
authors.initials: M
authors.lastname: Enomoto
authors.forename: Kumiko
authors.initials: K
authors.lastname: Furuki
authors.forename: Asuka
authors.initials: A
authors.lastname: Hino
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Shigeto
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Imaizumi
mesh_terms: D000368:Aged; D000428:Alcohol Drinking; D000704:Analysis of Variance; D001774:Blood Chemical Analysis; D001794:Blood Pressure; D015992:Body Mass Index; D049628:Body Size; D005260:Female; D017127:Glycation End Products, Advanced / Q000097:blood*; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood*; D012995:Solubility
chemical_list: D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic