Advanced glycation end products strongly activate platelets.
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.
Gawlowski
Thomas
T
Heart and Diabetes Center NRW, Ruhr-University Bochum, Georgstrasse 11, 32545, Bad Oeynhausen, Germany. tgawlowski@hdz-nrw.de
Stratmann
Bernd
B
Ruetter
Ruth
R
Buenting
Christina E
CE
Menart
Barbara
B
Weiss
Jürgen
J
Vlassara
Helen
H
Koschinsky
Theodor
T
Tschoepe
Diethelm
D
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
D015703:Antigens, CD; D015415:Biomarkers; C554586:CD63 protein, human; D017127:Glycation End Products, Advanced; D010980:Platelet Membrane Glycoproteins; D060149:Tetraspanin 30; D009113:Muramidase