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Platelet α 2 ‐adrenergic receptors in hypercholesterolemia: Relationship between binding studies and epinephrine‐induced platelet aggregation
Author(s) -
Baldassarre Damiano,
Mores Nadia,
Colli Susanna,
Pazzucconi Franco,
Sirtori Cesare R.,
Tremoli Elena
Publication year - 1997
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/s0009-9236(97)90104-1
Subject(s) - epinephrine , medicine , platelet , endocrinology , adrenergic receptor , familial hypercholesterolemia , receptor , platelet activation , chemistry , low density lipoprotein , cholesterol , alpha 2 adrenergic receptor
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 α 2 ‐adrenergic receptor density or affinity for epinephrine. Methods Platelet aggregation and binding studies, with use of [ 3 H]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 α 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. In 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 α 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. Clinical Pharmacology & Therapeutics (1997) 61 , 684–691; doi: