Plasma level of endogenous secretory RAGE is associated with components of the metabolic syndrome and atherosclerosis.
OBJECTIVE
Advanced glycation endproducts, AGEs, and its specific receptor, RAGE, are involved in diabetic vascular complications. Endogenous secretory RAGE, esRAGE, has been identified as an alternatively spliced form of RAGE, and shown to act as a decoy receptor for AGE. Here, we measured plasma esRAGE level with a recently developed enzyme-linked immunosorbent assay (ELISA) and examined its association with atherosclerosis in age- and gender-matched 203 type 2 diabetic and 134 nondiabetic subjects.


RESULTS
Plasma esRAGE was inversely associated with carotid or femoral atherosclerosis, as quantitatively measured as intimal-medial thickness (IMT) by arterial ultrasound. Stepwise regression analyses revealed that plasma esRAGE was the third strongest and independent factor associated with carotid IMT, following age and systolic blood pressure. Plasma esRAGE was significantly lower in diabetic patients (0.176+/-0.092 ng/mL) than nondiabetic controls (0.253+/-0.111). Of note, in all, diabetic or nondiabetic group, plasma esRAGE was significantly and inversely correlated with components of the metabolic syndrome including body mass index, blood pressure, triglyceride, HbA1c, or an insulin resistance index. Stepwise regression analyses showed that body mass index or insulin resistance index was the major factor determining plasma esRAGE in all, nondiabetic or diabetic population.


CONCLUSIONS
esRAGE is a novel and potential protective factor for the metabolic syndrome and atherosclerosis.
Koyama
Hidenori
H
Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan. hidekoyama@med.osaka-cu.ac.jp
Shoji
Takuhito
T
Yokoyama
Hisayo
H
Motoyama
Kohka
K
Mori
Katsuhito
K
Fukumoto
Shinya
S
Emoto
Masanori
M
Shoji
Tetsuo
T
Tamei
Hironori
H
Matsuki
Hirokazu
H
Sakurai
Shigeru
S
Yamamoto
Yasuhiko
Y
Yonekura
Hideto
H
Watanabe
Takuo
T
Yamamoto
Hiroshi
H
Nishizawa
Yoshiki
Y
D000328:Adult; D017677:Age Distribution; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D015992:Body Mass Index; D002339:Carotid Arteries / Q000000981:diagnostic imaging; D002340:Carotid Artery Diseases / Q000097:blood* / Q000000981:diagnostic imaging / Q000453:epidemiology*; D005260:Female; D005263:Femoral Artery / Q000000981:diagnostic imaging; D006801:Humans; D007333:Insulin Resistance; D016015:Logistic Models; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood* / Q000453:epidemiology*; D008875:Middle Aged; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood*; D012307:Risk Factors; D014463:Ultrasonography
D015415:Biomarkers; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic