Glycated albumin modulates platelet susceptibility to flow induced activation and aggregation.
A diabetic vasculature promotes cardiovascular diseases via endothelial cell activation induced by advanced glycation end products. It has recently become clear that activated platelets are a hallmark of cardiovascular disease and diabetes progression, by initiating and/or perpetuating the endothelial cell response. However, the role that platelets play in diabetic cardiovascular diseases remains elusive. Our objective was to evaluate the effects of glycated serum albumin on flow induced platelet activation and platelet aggregation. Albumin was glycated for up to 8 weeks. Timed samples of glycated or non-glycated albumin were removed to determine the effects of the extent of glycation on platelet functional changes. Thrombin receptor agonist peptide 6 (TRAP(6), residues 42-47 of the thrombin receptor) and collagen I induced platelet aggregation was measured as a time course of glycated albumin incubation. The thrombogenicity of platelets incubated with glycated albumin was also measured under static and dynamic flow conditions using the modified prothrombinase assay. CD41 and CD62P expression was examined using flow cytometry to validate aggregation and activation studies. Platelets subjected to glycated albumin were more susceptible to TRAP(6)- and collagen-induced aggregation and flow induced activation. The extent of albumin glycation modulates these changes. As the albumin glycation time increased, this enhancement in platelet function was more pronounced. These results indicate that under diabetic conditions activated platelets may act to promote cardiovascular disease progression.
School of Mechanical and Aerospace Engineering, Oklahoma State University, OK 74078-5016, USA. david.rubenstein@okstate.edu
David A
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D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D024042:Collagen Type I / Q000494:pharmacology; D005434:Flow Cytometry; D017127:Glycation End Products, Advanced; D006801:Humans; D066298:In Vitro Techniques; D009842:Oligopeptides / Q000494:pharmacology; D019007:P-Selectin / Q000097:blood; D015539:Platelet Activation / Q000187:drug effects / Q000502:physiology*; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology*; D040201:Platelet Membrane Glycoprotein IIb / Q000097:blood; D012709:Serum Albumin / Q000494:pharmacology* / Q000502:physiology; D013314:Stress, Mechanical; D000093423:Glycated Serum Albumin
D024042:Collagen Type I; D017127:Glycation End Products, Advanced; D009842:Oligopeptides; D019007:P-Selectin; D040201:Platelet Membrane Glycoprotein IIb; C504808:Ser-Phe-Phe-Leu-Arg-Asn; D012709:Serum Albumin; D000093423:Glycated Serum Albumin