Dietary alpha-linolenic acid increases the platelet count in ApoE mice by reducing clearance

We reported previously that dietary intake of alpha-linolenic acid (ALA) reduces atherogenesis and inhibits arterial thrombosis. Here, we analyze the substantial increase in the platelet count induced by ALA and the mechanisms of reduced platelet clearance. 8-week-old male apolipoprotein E knockout (ApoE) mice were fed a 0.21g% cholesterol diet complemented by either a high (7.3g%) or low ALA (0.03g%) content. Platelet counts doubled after 16 weeks ALA feeding, whereas the bleeding time remained similar. Plasma glycocalicin and glycocalicin index were reduced, while reticulated platelets, thrombopoietin and bone marrow megakaryocyte colony forming units remained unchanged. Platelet content of liver and spleen were substantially reduced, without affecting macrophage function and number. GPIb shedding, exposure of Pselectin and activated integrin αIIbβ3 upon activation with thrombin were reduced. Dietary ALA increased the platelet count by reducing their clearance in the RES. The latter appears to be mediated by reduced cleavage of GPIb by TACE, and reduced platelet activation/expression of procoagulant signaling. Ex vivo, there was less adhesion of human platelets to von Willebrand factor under high shear conditions after ALA treatment. Thus, ALA may be a promising tool in transfusion medicine and in high turnover/high activation platelet disorders. For personal use only. on August 31, 2017. by guest www.bloodjournal.org From