Apolipoprotein(a) Enhances Platelet Responses to the Thrombin Receptor-Activating Peptide SFLLRN

Elevated levels of lipoprotein(a) [Lp(a)] are correlated with an increased risk of atherosclerotic disease. We examined the effect of recombinant apolipoprotein(a) [r-apo(a)] and Lp(a) on responses of washed human platelets, prelabeled in the dense granules with [() C]serotonin and suspended in Tyrode's solution, to ADP and the thrombin receptor-activating peptide SFLLRN. No effect of the 17 kringle (K), 12K, or 6K r-apo(a) derivatives (at concentrations of 0.35 and 0.7 [micro sign]mol/L) or Lp(a) (up to 0.1 [micro sign]mol/L) on primary ADP-induced platelet aggregation was observed. In contrast, weak platelet responses stimulated by 7.5 [micro sign]mol/L SFLLRN were significantly enhanced by the r-apo(a) derivatives; eg, 0.7 [micro sign]mol/L 17K r-apo(a) increased aggregation from 15 +/- 4% to 58 +/- 6%, release of [() C]serotonin from 9 +/- 3% to 36 +/- 6%, and formation of thromboxane A2, measured as its stable metabolite thromboxane B2, from 7 +/- 1 to 29 +/- 5 ng/10 platelets (n=3; P