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. Increased platelet reactivity is one mechanism that may explain the enhanced risk of thromboembolism in hypercholesterolemia. This study assessed whether platelet hyperreactivity to epinephrine in hypercholesterolemia 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 platelets isolated from 30 patients with type IIa hypercholesterolemia and 23 control subjects. Results: Platelet aggregation in response to epinephrine was significantly higher in patients with hypercholesterolemia than in control subjects. A statistically significant higher alpha(2)-adrenergic receptor density was observed in a subgroup of 13 patients with hypercholesterolemia than in 13 sex- and age-matched control subjects (280 +/- 61 and 230 +/- 49 fmol/mg protein respectively; p < 0.03), but no difference was observed in receptor affinity for the ligand, Ln these subgroups plasma total and levels of low-density lipoprotein (LDL) cholesterol were inversely correlated with platelet aggregation but directly correlated with platelet receptor density. Conclusion: Platelet alpha(2)-adrenergic receptor density is increased in hypercholesterolemia and directly correlates with plasma total and levels of LDL cholesterol, providing at least a partial explanation for the enhanced platelet response to epinephrine that is observed in hypercholesterolemia.