Glycated Albumin Alters Platelet Activities Associated with Cardiovascular Diseases
Authors: Soaita Ioana , Yin Wei , Rubenstein David Alan 
Published: November 2023

Diabetes mellitus is characterized by prolonged high blood sugar levels, which can lead to the formation of advanced glycation end products (AGEs) in the blood. Albumin, the most abundant plasma protein, has a long residence time in plasma and a slow turn‐over rate, and thus has a higher probability of becoming glycosylated and interacting with cells and constituents of blood than most other plasma proteins. Due to the long residence time, albumin can exist in at least two glycosylated populations; reversibly glycated (those that have not passed through the Amadori rearrangement) and irreversibly glycated (those that have passed through the Amadori rearrangement). Recently, it has become clear that the effects of these two AGE populations on cells that are important to cardiovascular disease progression (platelets and endothelial cells) differ. Therefore, the aim of this project was to determine the effects of reversibly (less than 6 week exposure to glucose) and irreversibly glycated (greater than 6 week exposure to glucose) albumin on platelet activation, adhesion and aggregation processes, which have been closely associated with cardiovascular disease progression. Platelets were exposed to glycated albumin for various durations to elucidate a time‐course for observed changed. Enzyme‐linked immunosorbent assay (ELISA) and flow cytometry experiments were conducted to determine the magnitude of surface protein expression for proteins important for platelet adhesion to endothelial cells and the sub‐endothelial space. Additionally, aggregation agonist receptor expression was assessed and optical platelet aggregometry was used to confirm receptor sensitivity. Finally, platelet activation markers were assessed to correlate to previous work. Our data suggests that there was a significantly higher expression of the platelet α‐1 adrenergic, the PDY1 and the thromboxane A2 receptor after exposure to irreversibly glycated AGEs for longer durations. The activity of these receptors was confirmed with arachidonic acid antagonized aggregation. Additionally, platelet adhesion potential to endothelial cells (PECAM) and the sub‐endothelial space (GPIbα and GPIV) was also enhanced after exposure to irreversibly glycated AGEs for longer durations. Finally, the expression of platelet phosphatidylserine (quantified through Annexin V expression) was significantly enhanced after the exposure to any population of glycated albumin; supporting our previous work, which illustrated a heightened platelet activation potential. Combined our work suggests that the interaction between AGEs and platelets alters the three major facets of platelet activities that have been associated with cardiovascular disease progression. Additionally, these changes are only, for most of the responses, associated with exposure to irreversibly glycated albumin for longer durations. Thus, understanding the differences between reversibly glycated and irreversibly glycated albumin exposure on cells salient to cardiovascular disease progression, may provide important insight into disease progression and may help to identify new therapeutic targets for disease intervention.