In Vitro Glycoxidized Low-Density Lipoproteins and Low-Density Lipoproteins Isolated from Type 2 Diabetic Patients Activate Platelets via p38 Mitogen-Activated Protein Kinase

Context: Platelet hyperactivation contributes to the increased risk for atherothrombosis in type 2 diabetes and is associated with oxidative stress. Plasma low-density lipoproteins (LDLs) are exposed to both hyperglycemia and oxidative stress, and their role in platelet activation remains to be ascertained. Objective: The aim of this study was to investigate the effects of LDLs modified by both glycation and oxidation in vitro or in vivo on platelet arachidonic acid signaling cascade. The activation of platelet p38 MAPK, the stress kinase responsible for the activation of cytosolic phospholipase A2, and the concentration of thromboxane B2, the stable catabolite of the proaggregatory arachidonic acid metabolite thromboxane A2, were assessed. Results: First, in vitro-glycoxidized LDLs increased the phosphorylation of platelet p38 MAPK as well as the concentration of thromboxane B2. Second, LDLs isolated from plasma of poorly controlled type 2 diabetic patients stimulated both platelet p38 MAPK phosphorylati...