Alterations in platelet secretion differentially affect thrombosis and hemostasis.

Alterations in platelet secretion differentially affect thrombosis and hemostasis. Blood Adv. 2018 Sep 11;2(17):2187-2198 Authors: Joshi S, Banerjee M, Zhang J, Kesaraju A, Pokrovskaya ID, Storrie B, Whiteheart SW Abstract We genetically manipulated the major platelet vesicle-associated membrane proteins (VAMP2, VAMP3, and VAMP8) to create mice with varying degrees of disrupted platelet secretion. As previously shown, loss of VAMP8 reduced granule secretion, and this defect was exacerbated by further deletion of VAMP2 and VAMP3. VAMP2Δ3Δ8-/- platelets also had reduced VAMP7. Loss of VAMP2 and VAMP3 (VAMP2Δ3Δ) had a minimal impact on secretion when VAMP7 and VAMP8 were present. Integrin αIIbβ3 activation and aggregation were not affected, although spreading was reduced in VAMP2Δ3Δ8-/- platelets. Using these mice as tools, we asked how much secretion is needed for proper thrombosis and hemostasis in vivo. VAMP2Δ3Δ mice showed no deficiency, whereas VAMP8-/- mice had attenuated formation of occlusive thrombi upon FeCl3-induced arterial injury but no excessive bleeding upon tail transection. VAMP2Δ3Δ8-/- mice bled profusely and failed to form occlusive thrombi. Plasma-coagulation factors were normal in all of the strains, but phosphatidylserine exposure was reduced in VAMP2Δ3Δ and VAMP2Δ3Δ8-/- platelets. From our data, an ∼40% to 50% reduction in platelet secretion in vitro (dense and α granule) correlated with reduced...
Source: Adv Data - Category: Epidemiology Authors: Tags: Blood Adv Source Type: research