title: The AGE-RAGE Axis and Its Relationship to Markers of Cardiovascular Disease in Newly Diagnosed Diabetic Patients.
abstract: OBJECTIVE
  The purpose of the study was the simultaneous measurement of all the different components of the AGE-RAGE axis as well as several non-invasive markers of cardiovascular disease (CVD) in a cohort of newly diagnosed diabetic patients.
  
  
  METHODS
  In 80 newly diagnosed diabetic patients we measured serum carboxymethyllysine (CML), soluble RAGE (sRAGE) and peripheral mononuclear (PMNC) RAGE and AGER1 mRNA together with ICAM-1, VCAM-1, and malondialdehyde (MDA). We also assessed cardiovascular function by measurement of flow-mediated vasodilation (FMD), intima-media thickness (IMT) and arterial stiffness. Univariant correlation analysis was used to determine correlation between the variables in the study and multiple regression analysis was used to examine the association between the AGE-RAGE axis components and FMD, IMT and arterial stiffness.
  
  
  RESULTS
  Serum CML correlated positively with sRAGE, PMNC RAGE, HOMA-IR, ICAM-1, VCAM-1 and MDA, but inversely with PMNC AGER1. sRAGE and RAGE was positively correlated with AGER; IMT was positively correlated with HOMA-IR, ICAM-1, VCAM-1, MDA, and sRAGE and arterial stiffness had correlation with HOMA-IR, ICAM-1, VCAM-1, MDA, CML, sRAGE, AGER1 and RAGE. In multivariate analysis we found a significant relationship between CML with PMNC RAGE, HOMA-IR; sRAGE with VCAM-1 and MDA; PMNC RAGE with PMNC AGER1and CML; PMNC AGER1 with PMNC RAGE; FMD with sRAGE, CML and HbA1c; IMT with sRAGE, and arterial stiffness with sRAGE, sCML and AGER1.
  
  
  CONCLUSIONS
  We found significant and strong associations between the different components of the AGE-RAGE axis and also found significant association between AGE-RAGE axis markers, especially sRAGE with several noninvasive markers of cardiovascular disease risk. sRAGE, an easily measured parameter in blood, may potentially be used as a surrogate marker of AGEs-RAGE in patients with diabetes.
authors.affiliation: Department of Medical Science. Division of Health Science. University of Guanajuato Campus. León, Guanajuato, México.
authors.forename: Ma Etzabel
authors.initials: ME
authors.lastname: Villegas-Rodríguez
authors.affiliation: Department of Medicine. The Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Jaime
authors.initials: J
authors.lastname: Uribarri
authors.affiliation: Mexican Institute of Social Security. León, Guanajuato, México.
authors.forename: Sergio E
authors.initials: SE
authors.lastname: Solorio-Meza
authors.affiliation: Department of Medical Science. Division of Health Science. University of Guanajuato Campus. León, Guanajuato, México.
authors.forename: Martha E
authors.initials: ME
authors.lastname: Fajardo-Araujo
authors.affiliation: Department of Medicine. The Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Weijing
authors.initials: W
authors.lastname: Cai
authors.affiliation: Department of Medical Science. Division of Health Science. University of Guanajuato Campus. León, Guanajuato, México.
authors.forename: Sofía
authors.initials: S
authors.lastname: Torres-Graciano
authors.affiliation: Department of Medical Science. Division of Health Science. University of Guanajuato Campus. León, Guanajuato, México.
authors.forename: Rubén
authors.initials: R
authors.lastname: Rangel-Salazar
authors.affiliation: Department of Chemistry, University of Guanajuato, Guanajuato, Guanajuato, México.
authors.forename: Kazimierz
authors.initials: K
authors.lastname: Wrobel
authors.affiliation: Department of Medical Science. Division of Health Science. University of Guanajuato Campus. León, Guanajuato, México.
authors.forename: Ma Eugenia
authors.initials: ME
authors.lastname: Garay-Sevilla
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood* / Q000473:pathology; D059168:Carotid Intima-Media Thickness; D003920:Diabetes Mellitus / Q000097:blood* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000097:blood*; D012307:Risk Factors; D059289:Vascular Stiffness
chemical_list: D000951:Antigens, Neoplasm; D015415:Biomarkers; D001798:Blood Proteins; C498978:MOK protein, human; D020928:Mitogen-Activated Protein Kinases