title: Advanced glycation end products strongly activate platelets.
abstract: BACKGROUND
  Diabetes mellitus is characterized by hyperglycemia that plays an important role in the pathogenesis of diabetic complications including cardiovascular diseases. Moreover, hyperglycemia induces increased generation of advanced glycation end products (AGEs). The activation of platelets is associated with the development of cardiovascular diseases.
  
  
  OBJECTIVE
  The question whether AGEs acutely induce platelet activation as a response to exogenous stimulus is addressed.
  
  
  METHODS
  The effect of AGEs derived from food and human serum being purified by lysozyme affinity chromatography was examined by incubating in vitro freshly isolated blood platelets from fasted subjects at various concentrations and different time points. Platelet activation, determined as expression of surface markers CD62 and CD63, and the presence of the receptor for AGEs (RAGE) in platelet membranes was measured by flow cytometric analysis using specific antibodies.
  
  
  RESULTS
  Incubation with food-derived as well as serum-derived AGEs stimulated significantly the expression of CD62 up to 7.1-fold and CD63 up to 2.2-fold at the platelet surface membrane as a function of concentration and time. Incubation with thrombin or AGEs significantly increased RAGE expression twofold at the platelet surface membrane.
  
  
  CONCLUSIONS
  The increase in surface activation marker and RAGE expression in platelets, resulting from concentrations of AGEs that occur in vivo after a meal or a drink as a source of exogenous AGEs, points to signaling mechanisms for food AGEs that could favor the precipitation of acute postprandial ischemic events.
authors.affiliation: Heart and Diabetes Center NRW, Ruhr-University Bochum, Georgstrasse 11, 32545, Bad Oeynhausen, Germany. tgawlowski@hdz-nrw.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Gawlowski
authors.forename: Bernd
authors.initials: B
authors.lastname: Stratmann
authors.forename: Ruth
authors.initials: R
authors.lastname: Ruetter
authors.forename: Christina E
authors.initials: CE
authors.lastname: Buenting
authors.forename: Barbara
authors.initials: B
authors.lastname: Menart
authors.forename: Jürgen
authors.initials: J
authors.lastname: Weiss
authors.forename: Helen
authors.initials: H
authors.lastname: Vlassara
authors.forename: Theodor
authors.initials: T
authors.lastname: Koschinsky
authors.forename: Diethelm
authors.initials: D
authors.lastname: Tschoepe
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000187:drug effects* / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D002846:Chromatography, Affinity; D048909:Diabetes Complications / Q000378:metabolism; D003920:Diabetes Mellitus / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D017127:Glycation End Products, Advanced / Q000097:blood / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009113:Muramidase / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D060149:Tetraspanin 30; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; C554586:CD63 protein, human; D017127:Glycation End Products, Advanced; D010980:Platelet Membrane Glycoproteins; D060149:Tetraspanin 30; D009113:Muramidase