Inhibition of platelet GPIIb–IIIa and P-selectin expression by aspirin is impaired by stress hyperglycemia

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Increased aspirin resistance may contribute to the increase in thrombotic events observed in patients with type 2 diabetes. In this study, we examined if acute exposure to increased plasma glucose impaired the inhibitory effects of aspirin on platelet activation. Whole-blood samples were incubated with 100 (euglycemia), 200, 300, and 600 mg/dl glucose followed by incubation with aspirin [acetylsalicylic acid (ASA)]. Using flow cytometry, GPIIb–IIIa and P-selectin were analyzed in unstimulated and arachidonic acid (AA)-stimulated platelets. In euglycemic blood, AA caused a significant increase in platelet GPIIb–IIIa expression [unstimulated: 59.5±8.2 total fluorescence intensity (TFI), AA stimulated: 319.6±42.7 TFI, P=.002] and P-selectin (4.4±0.7 and 179.5±38.5 TFI, P<.001). In vitro, ASA significantly inhibited both GPIIb–IIIa expression (36.5%) and P-selectin expression (81%; P<.005). However, increased blood glucose (200 mg/dl) significantly impaired the inhibitory effect of ASA (84% for GPIIb–IIIa, P<.005; 48% for P-selectin, P=NS). Increasing glucose to 600 mg/dl completely overwhelmed the inhibitory effect of ASA. A statistically significant interaction between glucose concentration and ASA dose was found ( P<.001 for GPIIb–IIIa and P=.004 for P-selectin). In vitro, concentration-dependent stress hyperglycemia significantly impaired the inhibitory effects of aspirin on human platelet GPIIb–IIIa and P-selectin expression. Under acute hyperglycemic conditions, the effectiveness of ASA to inhibit platelets via the AA-activation pathway may be significantly reduced.