PLATELET ALPHA(2)-ADRENERGIC RECEPTORS IN HYPERCHOLESTEROLEMIA - RELATIONSHIP BETWEEN BINDING-STUDIES AND EPINEPHRINE-INDUCED PLATELET-AGGREGATION

Background: Platelets isolated from patients with hypercholesterolemia are more sensitive in vitro to various aggregating agents, including epinephrine, than those isolated from normocholesterolemic subjects. I ncreased platelet reactivity is one mechanism that may explain the enh anced risk of thromboembolism in hypercholesterolemia. This study asse ssed whether platelet hyperreactivity to epinephrine in hypercholester olemia is associated with higher alpha(2)-adrenergic receptor density or affinity for epinephrine. Methods: Platelet aggregation and binding studies, with use of [H-3]yohimbine as Ligand, were performed on plat elets isolated from 30 patients with type IIa hypercholesterolemia and 23 control subjects. Results: Platelet aggregation in response to epi nephrine was significantly higher in patients with hypercholesterolemi a than in control subjects. A statistically significant higher alpha(2 )-adrenergic receptor density was observed in a subgroup of 13 patient s with hypercholesterolemia than in 13 sex- and age-matched control su bjects (280 +/- 61 and 230 +/- 49 fmol/mg protein respectively; p < 0. 03), but no difference was observed in receptor affinity for the ligan d, Ln these subgroups plasma total and levels of low-density lipoprote in (LDL) cholesterol were inversely correlated with platelet aggregati on but directly correlated with platelet receptor density. Conclusion: Platelet alpha(2)-adrenergic receptor density is increased in hyperch olesterolemia and directly correlates with plasma total and levels of LDL cholesterol, providing at least a partial explanation for the enha nced platelet response to epinephrine that is observed in hypercholest erolemia.