Advanced Glycation End Products Alters Platelet Aggregation

Abstract

Diabetes mellitus is in part characterized through the presence of advanced glycation end products (AGEs) within the cardiovascular system. AGEs are a heterogeneous population of glycated proteins, lipids or other molecules. Albumin is the plasma protein that is most susceptible to glycation due to its long residence time in plasma. Thus, we aimed to evaluate the effects of reversibly and irreversibly glycated albumin on platelet aggregation towards arachadonic acid, epinephrine and ADP and to determine mechanisms responsible for altered aggregation. Previous work from our group has shown that the presence of AGEs antagonizes thrombin and collagen mediated aggregation by up‐regulating GPIIb/IIIa. We hypothesized that irreversibly glycated albumin would activate the arachadonic acid, epinephrine and ADP pathways, more so than reversibly glycated albumin and non‐glycated albumin and that this would at least be partially mediated through an enhanced expression of GPIIb/IIIa. Additionally, with longer exposure durations, we expected a further enhancement of the aggregation system as compared with shorter exposure durations. Our results suggest that irreversibly glycated albumin is more detrimental to platelet functions than reversibly or non‐glycated albumin, but in general the exposure duration, which was up to 4 hours, did not play a significant role in altered aggregation. In particular, both the rate by which platelets aggregate and the quantity of platelets participating in aggregation was enhanced after exposure to irreversibly glycated albumin. These data suggest that the presence of irreversibly glycated albumin can significant alter platelet functions in diabetics, which may serve as a link between enhanced cardiovascular disease progressions in diabetic populations.