Inhibition of ADP-induced platelet aggregation by apoE is not mediated by membrane cholesterol depletion.

We have previously shown that plasma HDL-E, a minor subclass of high-density lipoproteins (HDL) containing apolipoprotein (apo) E, has a potent anti-platelet effect and implicated apoE as the active constituent. Recently, apoE complexes with phospholipids (DMPC) were reported to inhibit thrombin-induced aggregation by sequestering platelet membrane cholesterol. Here we demonstrate that platelet cholesterol depletion is an improbable explanation for the suppressive effect of apoE:DMPC on ADP-mediated platelet aggregation; only 0.5% of cholesterol was released prior to addition of ADP to initiate aggregation while lactoferrin, which does not accept cellular cholesterol, was also inhibitory. Previous studies have shown that apoE and lactoferrin are both bound by platelets but whether this provides the initial stimulus for suppression of aggregation remains to be established.