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.
Aim of the study
The question whether AGEs acutely induce platelet activation
as a response to exogenous stimulus is addressed.
Materials and 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.