title: Two soluble isoforms of receptors for advanced glycation end products (RAGE) in carotid atherosclerosis: the difference of soluble and endogenous secretory RAGE.
abstract: BACKGROUND
  Advanced glycation end products (AGEs) promote atherosclerosis through binding to their receptor, RAGE. Since soluble RAGE (sRAGE) and endogenous secretory RAGE (esRAGE) may suppress AGEs-RAGE signaling, we examined the usefulness of sRAGE and esRAGE as biomarkers of early-stage atherosclerosis.
  
  
  METHODS
  Serum sRAGE and esRAGE levels were measured in 284 subjects with no history of atherothrombotic diseases. The subjects were divided into high-sRAGE and low-sRAGE groups and high-esRAGE and low-esRAGE groups based on respective median values. We investigated the relationships between these parameters and the following factors: number of metabolic components, maximum intima-media thickness of the common carotid artery (IMT Cmax), carotid plaque calcification, and asymptomatic cerebral white matter lesions.
  
  
  RESULTS
  The low-sRAGE and low-esRAGE groups exhibited significantly more components of metabolic syndrome than the high-sRAGE and high-esRAGE groups, respectively. IMT Cmax was significantly higher in the low-sRAGE and low-esRAGE groups. Low-sRAGE levels were significantly associated with carotid plaque calcification. Multiple linear regression analysis identified body mass index (BMI), age, and high-sensitivity C-reactive protein as determinants of sRAGE, whereas only BMI was identified as a determinant of esRAGE.
  
  
  CONCLUSIONS
  We demonstrated that sRAGE and esRAGE are associated with atherosclerotic risk factors in early-stage atherosclerosis, suggesting that their levels evolve in correlation with those of metabolic components and inflammation. Interestingly, low-sRAGE and esRAGE levels are associated with high IMT Cmax, but only low-sRAGE levels were associated with carotid plaque calcification. Thus, sRAGE and esRAGE may reflect different aspects of atherosclerosis in its early stage.
authors.affiliation: Department of Neurology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Moriya
authors.affiliation: Department of Neurology, Tokyo Women's Medical University, Tokyo, Japan. Electronic address: myamazak@nij.twmu.ac.jp.
authors.forename: Masako
authors.initials: M
authors.lastname: Yamazaki
authors.affiliation: Toda Chuo Health Exam Center, Saitama, Japan.
authors.forename: Hirohiko
authors.initials: H
authors.lastname: Murakami
authors.affiliation: Department of Neurology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Maruyama
authors.affiliation: Department of Neurology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Uchiyama
mesh_terms: D000367:Age Factors; D000368:Aged; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000032:analysis; D002340:Carotid Artery Diseases / Q000097:blood* / Q000473:pathology; D017536:Carotid Artery, Common / Q000473:pathology*; D059168:Carotid Intima-Media Thickness; D016893:Carotid Stenosis / Q000097:blood / Q000473:pathology; D005260:Female; D017127:Glycation End Products, Advanced / Q000097:blood* / Q000145:classification; D006801:Humans; D016014:Linear Models; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000473:pathology; D008875:Middle Aged; D020033:Protein Isoforms; D012307:Risk Factors; D061205:Vascular Calcification / Q000097:blood / Q000473:pathology
chemical_list: D015415:Biomarkers; D017127:Glycation End Products, Advanced; D020033:Protein Isoforms; D002097:C-Reactive Protein
keywords: Soluble receptor for advanced glycation end products; calcification; carotid atherosclerosis; endogenous secretory receptor for advanced glycation end products; intima-media thickness; metabolic component