title: Ratio of serum levels of AGEs to soluble form of RAGE is a predictor of endothelial function.
abstract: OBJECTIVE
  Advanced glycation end products (AGEs) and their specific receptor, the receptor for AGEs (RAGE), play an important role in atherosclerosis. Recently, a soluble form of RAGE (sRAGE) has been identified in human serum. However, the role of sRAGE in cardiovascular disease is still controversial. There is no information on the association between simultaneous measurements of AGEs and sRAGE and vascular function. In this study, we evaluated the associations between serum levels of AGEs and sRAGE, ratio of AGEs to sRAGE, and vascular function.
  
  
  METHODS
  We measured serum levels of AGEs and sRAGE and assessed vascular function by measurement of flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation in 110 subjects who underwent health examinations. Multivariate regression analyses were performed to identify factors associated with vascular function.
  
  
  RESULTS
  Univariate regression analysis revealed that FMD correlated with age, BMI, systolic blood pressure, diastolic blood pressure, heart rate, triglycerides, HDL cholesterol, glucose, smoking pack-years, nitroglycerine-induced vasodilation, serum levels of AGEs and sRAGE, and ratio of AGEs to sRAGE. Multivariate analysis revealed that the ratio of AGEs to sRAGE remained an independent predictor of FMD, while serum level of AGEs alone or sRAGE alone was not associated with FMD.
  
  
  CONCLUSIONS
  These findings suggest that sRAGE may have a counterregulatory mechanism that is activated to counteract the vasotoxic effect of the AGE-RAGE axis. The ratio of AGEs to sRAGE may be a new chemical biomarker of endothelial function.
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Kajikawa
authors.affiliation: Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan.
authors.forename: Ayumu
authors.initials: A
authors.lastname: Nakashima
authors.affiliation: Department of Cardiology, Chugoku Rosai Hospital, Hiroshima, Japan.
authors.forename: Noritaka
authors.initials: N
authors.lastname: Fujimura
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Maruhashi
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Iwamoto
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Akimichi
authors.initials: A
authors.lastname: Iwamoto
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Matsumoto
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Nozomu
authors.initials: N
authors.lastname: Oda
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Hidaka
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Yasuki
authors.initials: Y
authors.lastname: Kihara
authors.affiliation: Department of Gastroenterology and Metabolism, Institute of Biomedical and Health Sciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
authors.affiliation: Hiroshima International University, Hiroshima, Japan.
authors.forename: Chikara
authors.initials: C
authors.lastname: Goto
authors.affiliation: Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Aibara
authors.affiliation: Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Noma
authors.affiliation: Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University, Ishikawa, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Takeuchi
authors.affiliation: Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Matsui
authors.affiliation: Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Sho-Ichi
authors.initials: S
authors.lastname: Yamagishi
authors.affiliation: Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan yhigashi@hiroshima-u.ac.jp.
authors.forename: Yukihito
authors.initials: Y
authors.lastname: Higashi
mesh_terms: D000368:Aged; D050197:Atherosclerosis / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003430:Cross-Sectional Studies; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood*; D012044:Regression Analysis; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood; D014664:Vasodilation
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D006442:Glycated Hemoglobin; D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D014280:Triglycerides