Platelet resistance to the antiaggregatory cyclic nucleotides in central obesity involves reduced phosphorylation of vasodilator-stimulated phosphoprotein

Isabella Russo, Paola Del Mese, Gabriella Doronzo, Alessandro De Salve, Mariantonietta Secchi, Mariella Trovati, Giovanni Anfossi

Research output: Contribution to journalArticle

Abstract

Background: Impairment of platelet response to antiaggregatory agents is seen in individuals with central obesity and may play a role in the increased cardiovascular risk associated with obesity. In this study we evaluated whether this impairment involves the antiaggregatory pathways regulated by cAMP and cGMP. Methods: We obtained platelet-rich plasma from 12 obese individuals and 12 controls. We investigated the effects of the cyclic nucleotide analogs 8-pCPT-cAMP (10-500 μmol/L) and 8-pCPT-cGMP (10-500 μmol/L) on ADP-induced platelet aggregation as assessed by decreased light scattering. We assessed the activation of cAMP- and cGMP-dependent protein kinases by measuring phosphorylation of the vasodilator-stimulated phosphoprotein (VASP) at Ser157 and Ser239. Results: The antiaggregatory effect of both cyclic nucleotide analogs was impaired in obese individuals compared to controls, with mean (SE) half-maximal inhibitory concentrations (IC50) (after 20-min incubation) of 123 (33) μmol/L vs 5 (1) μmol/L, respectively, for 8-pCPT-cAMP (P 50. In obese individuals, VASP phosphorylation at Ser157 and Ser239 in response to cyclic nucleotides was significantly lower than in controls. Conclusions: In central obesity the reduced ability of cyclic nucleotides to inhibit platelet aggregation is associated with reduced activation of their specific kinases. Because cyclic nucleotides help regulate platelet antiaggregation, alteration of this ability is consistent with platelet hyperactivity in obesity.

Original languageEnglish
Pages (from-to)1053-1060
Number of pages8
JournalClinical Chemistry
Volume53
Issue number6
DOIs
Publication statusPublished - Jun 2007

ASJC Scopus subject areas

  • Clinical Biochemistry

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