Apolipoprotein C3 (apoC3) circulates primarily on triglyceride-rich lipoproteins and promotes atherosclerosis by fostering lipidemia and inflammation. Thus, apoC3 represents an important cardiovascula Show more
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. We aimed to elucidate the impact of apoC3 on prothrombotic platelet functions. Platelets were isolated from healthy volunteers and the effect of apoC3 on their activation and aggregation was assessed by flow cytometry, ELISA, and light transmission and multiple electrode aggregometry. Platelet spreading and cytoskeletal remodeling were examined by immunofluorescence microscopy. In vivo relevance was confirmed in a murine model of FeCl ApoC3 strongly reduced platelet aggregation independently of the presence of plasma or other blood cells and impaired both α 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. Show less