This study showed that decreased antiaggregatory action of the cyclic nucleotides cAMP and cGMP in platelets of individuals with central obesity was associated with decreased phosphorylation of VASP at specific sites, reflecting impaired activation of PKA and PKG.
50], values of both cyclic nucleotide analogs remained significantly correlated with HONIA IR, thus suggesting that the molecular defect involved in the resistance to cyclic nucleotides is directly related to insulin resistance.
The reduced antiaggregatory effects of insulin, organic nitrates, and prostacyclin, which act through activation of cyclic nucleotide /protein kinase pathways (10, 11), may be explained, at least in part, by an impaired action of the cyclic nucleotides on their specific kinases.
The present results also show impaired ability of cyclic nucleotides themselves to activate downstream steps of antiaggregation, such as those related to VASP phosphorylation.
Impaired synthesis and action of antiaggregating cyclic nucleotides in platelets from obese subjects: possible role in platelet hyperactivation in obesity.
VASP is considered a reliable mediator of cyclic nucleotide action (12, 24, 25).