Lipoprotein (a) reduces platelet aggregation via apo(a)-mediated decreases in thromboxane A(2)production.
Agonist (collagen- or ADP-)-stimulated platelet aggregation and thromboxane B(2) (T X B(2) ) production was reduced in human whole blood (WB) and washed platelets (WP) that were co-incubated with lipoprotein (a)[Lp(a)] at levels of 25, 50 and 100 mg % but not at 5 mg % relative to a baseline concentration of 1 mg %. Significant decreases in agonist-stimulated aggregation and T X B(2) levels were seen with 5, 25, 50 and 100 mg %purified apo (a) that was co-incubated with WB and WP relative to a baseline concentration of 1 mg %. Purified Lp(a) that was free of apo(a) [Lp(a)(-)], at concentrations of 5, 25, 50 and 100 mg %, that were co-incubated with WB and WP, had no impact on agonist-induced platelet aggregation and T X B(2) production relative to a baseline level of 1 mg %. A monoclonal antibody (Mab) (3B1) against apo(a) blocked Lp(a)-mediated reduction in platelet aggregation and T X B(2) concentrations in WB and WP that were stimulated by either agonist. Various Mabs against apoB failed to affect an Lp(a)-induced reduction in WB and WP aggregation or T X B(2) levels in response to either agonist. These results strongly suggest that Lp(a)-induced decreases in collagen or ADP stimulated platelet aggregation and T X B(2) production are mediated by apo(a).
Barre
D E
DE
Baxter Healthcare Corporation, Renal Research Division, MPR-R2, 1620 Waukegan Road, McGaw Park, IL 60085, USA.