title: Inhibition of platelet GPIIb-IIIa and P-selectin expression by aspirin is impaired by stress hyperglycemia.
abstract: 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.
authors.affiliation: Cardiovascular and Thoracic Surgery and the Sarver Heart Center, University of Arizona Health Sciences Center, Tucson, AZ 85724, USA.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Le Guyader
authors.forename: Garrett
authors.initials: G
authors.lastname: Pacheco
authors.forename: Norma
authors.initials: N
authors.lastname: Seaver
authors.forename: Grace
authors.initials: G
authors.lastname: Davis-Gorman
authors.forename: Jack
authors.initials: J
authors.lastname: Copeland
authors.forename: Paul F
authors.initials: PF
authors.lastname: McDonagh
mesh_terms: D000328:Adult; D001241:Aspirin / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism*; D019007:P-Selectin / Q000378:metabolism*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism*; D013312:Stress, Physiological / Q000187:drug effects*
chemical_list: D001786:Blood Glucose; D019007:P-Selectin; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D001241:Aspirin