Elevated levels of apolipoprotein C3 impair platelet function and reduce thrombosis

BACKGROUND: Apolipoprotein C3 (apoC3) circulates primarily on triglyceride-rich lipoproteins and promotes atherosclerosis by fostering lipidemia and inflammation. Thus, apoC3 represents an important cardiovascular risk factor and is associated with cardiovascular events and mortality. Due to their dual nature as hemostatic and immunomodulatory effector cells, platelets play an important role in the development and progression of atherosclerosis and are responsible for thrombotic/thromboembolic events upon plaque rupture. OBJECTIVES: We aimed to elucidate the impact of apoC3 on prothrombotic platelet functions. METHODS: -induced thrombosis. RESULTS: activation and degranulation. While agonist-induced calcium mobilization, hyperpolarization, and membrane fluidity were not affected, apoC3 slightly reduced AKT phosphorylation and increased vasodilator-stimulated phosphoprotein (VASP) phosphorylation. Furthermore, apoC3-treated platelets displayed impaired lamellipodia formation, which was accompanied by aberrant actin cytoskeleton remodeling. Finally, transfusion of apoC3-treated platelets into mice delayed thrombus formation in vivo. CONCLUSION: We identified apoC3 as lipoprotein-derived inhibitor of prothrombotic platelet functions, mediating antiaggregatory effects, likely via modulating AKT and VASP signaling and interfering with actin cytoskeleton remodeling to impair lamellipodia formation. Thus, apoC3 may counterbalance its proatherogenic properties on lipid metabolism and inflammation by dampening thrombotic risk in hyperlipidemia.