Synergistic phosphorylation of the focal adhesion-associated vasodilator-stimulated phosphoprotein in intact human platelets in response to cGMP- and cAMP-elevating platelet inhibitors

Platelet Resistance to the Antiaggregatory Cyclic Nucleotides in Central Obesity Involves Reduced Phosphorylation of Vasodilator-Stimulated Phosphoprotein

“…Platelet counts were determined on an S-plus Coulter Counter (Coulter Electronics). Mean (SE) platelet counts in PRP (10 9 /L) were 268 (25) in controls and 248 (18) in obese individuals (not significant). Because the study design consisted of measurement of platelet responses in samples from the same PRP after addition of buffer solutions or different substances for each study participant, platelet numbers were not adjusted.…”

“…VASP phosphorylation closely correlates with inhibition of fibrinogen binding to glycoprotein IIb/IIIa (GP IIb/IIIa) (18,24 ), and it affects initial sequences of platelet adhesion and activation by modulating interactions of platelet actin filaments (4,19 ). VASP is considered a reliable mediator of cyclic nucleotide action (12,24,25 ).…”

cGMP-Dependent Protein Kinases and cGMP Phosphodiesterases in Nitric Oxide and cGMP Action

“…VASP is phosphorylated by PKG and PKA (Walter and Gambaryan, 2009); PKGI preferentially phosphorylates VASP at Ser-239. Phosphorylation of VASP is correlated with 1) changes in platelet cytoskeletal organization, 2) inhibition of platelet activation Nolte et al, 1994), 3) decreased association of VASP with F-actin and VASP-driven actin filament formation (Benz et al, 2008;Benz et al, 2009), 4) enhanced angiogenesis (Chen et al, 2004(Chen et al, , 2008, and 5) induction of long-term potentiation . Increased phosphorylation of VASP also causes a change in its intracellular location Walter and Gambaryan, 2009).…”

Dipyridamole Enhances NO/cGMP-Mediated Vasodilator-Stimulated Phosphoprotein Phosphorylation and Signaling in Human Platelets

“…The most important inhibitory endotheliumderived factors are NO and prostaglandin I 2 (PGI 2 ), which inhibit platelets by increasing the level of intracellular cyclic nucleotides. 4,5 Subsequent stimulation of cGMP-and cAMPdependent protein kinases leads to the phosphorylation of a variety of proteins. 6 In platelets, this inhibits agoniststimulated calcium signaling, 7,8 fibrinogen binding, 9 adhesion, 10 and aggregation 5 and stimulates phosphorylation of the cytoskeletal and focal adhesion protein vasodilatorstimulated phosphoprotein (VASP).…”