LIPOPROTEIN(A) INHIBITS COLLAGEN-INDUCED AGGREGATION OF THROMBOCYTES

Lipoprotein(a) [Lp(a)] is known to interact with human platelets in vi tro. In the present study the effect of physiological concentrations o f Lp(a) on platelet aggregation was studied. Freshly prepared gel-filt ered platelets from healthy donors were incubated for 30 minutes at 37 degrees C with various concentrations of Lp(a); aggregation was trigg ered with ADP, thrombin, and collagen. Control incubations were perfor med with Tyrode's solution or LDL. Thrombin- and ADP-triggered aggrega tions were only slightly influenced by Lp(a), but aggregation of plate lets stimulated with collagen (4 mu g/mL) was markedly inhibited. Meas urable effects occurred at low concentrations (0.05 mg/mL) of total Lp (a); at 0.5 mg/mL, maximum aggregation of platelets was inhibited by 5 4+/-20%, and the aggregation rate was attenuated by 47+/-19% compared with platelets incubated with Tyrode's solution. Preincubation of coll agen (4 mu g/mL) with Lp(a) yielded similar results. The effect of Lp( a) on platelet aggregation was accompanied by a significant reduction of serotonin release and TXA(2) formation. Higher concentrations of co llagen (greater than or equal to 10 mu g/mL) caused the inhibitory eff ect of Lp(a) on collagen-induced aggregation to disappear. In contrast , incubation of platelets with 5 mg/mL LDL led to a significant increa se of aggregation rate, maximum aggregation, serotonin release, and fo rmation of TXA(2) when aggregation was induced with 4 mu g/mL collagen . In an adhesion assay using fresh whole blood, which mimics the in vi vo situation of vessel injury, Lp(a) reduced platelet adhesion at shea r rates of 300 and 1600/s by 22.6% and 11.6%, respectively, In additio n, Lp(a) reduced the size of platelet aggregates significantly (up to 63%); this reduction was more distinct at the higher shear rate. Unlik e LDL, Lp(a) is not a proaggregatory lipoprotein; rather, collagen-tri ggered aggregation in vitro is attenuated by Lp(a).