| Autor: |
Russo, Isabella, Viretto, Michela, Barale, Cristina, Mattiello, Luigi, Doronzo, Gabriella, Pagliarino, Andrea, Cavalot, Franco, Trovati, Mariella, Anfossi, Giovanni |
| Předmět: |
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| Zdroj: |
Diabetes; Nov2012, Vol. 61 Issue 11, p2913-2921, 9p, 7 Graphs |
| Abstrakt: |
Since hyperglycemia is involved in the "aspirin resistance" occurring in diabetes, we aimed at evaluating whether high glucose interferes with the aspirin-induced inhibition of thromboxane synthesis and/or activation of the nitric oxide (NO)/cGMP/cGMPdependent protein kinase (PKG) pathway in platelets. For this purpose, in platelets from 60 healthy volunteers incubated for 60 min with 5-25 mmol/L D-glucose or iso-osmolar mannitol, we evaluated the influence of a 30-min incubation with lysine acetylsalicylate (L-ASA; 1-300 mmol/L) on 1) platelet function under shear stress; 2) aggregation induced by sodium arachidonate or ADP; 3) agonist-induced thromboxane production; and 4) NO production, cGMP synthesis, and PKG-induced vasodilator-stimulated phosphoprotein phosphorylation. Experiments were repeated in the presence of the antioxidant agent amifostine. We observed that platelet exposure to 25 mmol/L D-glucose, but not to isoosmolar mannitol, 1) reduced the ability of L-ASA to inhibit platelet responses to agonists; 2) did not modify the L-ASA--induced inhibition of thromboxane synthesis; and 3) prevented the L-ASA--induced activation of the NO/cGMP/PKG pathway. Preincubation with amifostine reversed the high-glucose effects. Thus, high glucose acutely reduces the antiaggregating effect of aspirin, does not modify the aspirin-induced inhibition of thromboxane synthesis, and inhibits the aspirin-induced activation of the NO/ cGMP/PKG pathway. These results identify a mechanism by which high glucose interferes with the aspirin action. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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