The vasodilator-stimulated phosphoprotein (VASP) is involved in cGMP- and cAMP-mediated inhibition of agonist-induced platelet aggregation, but is dispensable for smooth muscle function

The vasodilator-stimulated phosphoprotein (VASP) is associated with actin f ilaments and focal adhesions, which form the interface between the cytoskel eton and the extracellular matrix. VASP is phosphorylated by both the cAMP- and cGMP-dependent protein kinases in a variety of cells, including platel ets and smooth muscle cells, Since both the cAMP and cGMP signalling cascad es relax smooth muscle and inhibit platelet activation, it was speculated t hat VASP mediates these effects by modulating actin filament dynamics and i ntegrin activation. To study the physiological relevance of VASP in these p rocesses, we inactivated the VASP gene in mice. Adult VASP-deficient mice h ad normal agonist-induced contraction, and normal cAMP- and cGMP-dependent relaxation of intestinal and vascular smooth muscle, In contrast, cAMP- and cGMP-mediated inhibition of platelet aggregation was significantly reduced in the absence of VASP, Other cAMP- and cGMP-dependent effects in platelet s, such as inhibition of agonist-induced increases in cytosolic calcium con centrations and granule secretion, were not dependent on the presence of VA SP, Our data show that two different cyclic, nucleotide-dependent mechanism s are operating during platelet activation: a VASP-independent mechanism fo r inhibition of calcium mobilization and granule release and a VASP-depende nt mechanism for inhibition of platelet aggregation which may involve regul ation of integrin function.