title: Etofibrate increases binding of low and high density lipoprotein to human platelets of patients with type II hyperlipoproteinemia.
abstract: Previous work suggested an influence of etofibrate, a diester of nicotinic acid and clofibric acid, on lipoprotein receptors. Besides its beneficial effects on plasma lipoprotein levels of decrease in total cholesterol, LDL-cholesterol and triglycerides and increase in HDL-cholesterol, etofibrate was shown to inhibit platelet function. In order to further evaluate platelet-lipoprotein interactions, the effects of etofibrate on plasma lipids and lipoproteins on the specific binding of normal [111In]LDL and [111In]HDL onto platelets as well as its effect on platelet function were evaluated in 8 patients affected by Type II hyperlipoproteinemia (HLP). In all patients binding was saturable and indicated high affinity binding sites capable of binding 927 +/- 233 ng protein of [111In]LDL/10(9) platelets (Kd 12 +/- 3 micrograms protein/ml) and 1496 +/- 435 ng protein of [111In]HDL/10(9) platelets (Kd 14 +/- 3 micrograms protein/ml). The capacity of native LDL (HDL) to displace bound [111In]LDL ([111In]HDL) by half (IC50) amounted to 22 +/- 9 micrograms protein/ml (26 +/- 8 micrograms protein/ml). Following a 6-week treatment period with etofibrate (500 mg twice daily), decrease in plasma total cholesterol, LDL-cholesterol and apolipoprotein (apo) B and increase in HDL-cholesterol and apo AI was correlated to a significant (P < 0.01) increase in LDL- as well as HDL-receptor binding. The platelet binding capacity increased to 1085 +/- 212 ng protein/10(9) platelets (Kd 8 +/- 3 micrograms protein/ml) for [111In]LDL and to 1867 +/- 266 ng protein/10(9) platelets for [111In]HDL (Kd 11 +/- 3 micrograms protein/ml). Platelet function studies demonstrated significantly (P < 0.01) reduced platelet aggregation in response to ADP and thromboxane formation after 6 weeks of etofibrate therapy. These findings in patients with HPL Type II indicate in vivo upregulation of specific [111In]LDL as well as [111In]HDL binding sites on human platelets associated with reduced platelet activation following etofibrate therapy.
authors.affiliation: Department of Nuclear Medicine, University of Vienna, Austria.
authors.forename: I
authors.initials: I
authors.lastname: Virgolini
authors.forename: E
authors.initials: E
authors.lastname: Koller
authors.forename: S
authors.initials: S
authors.lastname: Li
authors.forename: Q
authors.initials: Q
authors.lastname: Yang
authors.forename: M
authors.initials: M
authors.lastname: Banyai
authors.forename: F
authors.initials: F
authors.lastname: Rauscha
authors.forename: J
authors.initials: J
authors.lastname: Pidlich
authors.forename: W
authors.initials: W
authors.lastname: Pirker
authors.forename: H
authors.initials: H
authors.lastname: Sinzinger
mesh_terms: D000328:Adult; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001055:Apolipoproteins B / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D002995:Clofibric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D008075:Lipoproteins, HDL / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D013268:Stimulation, Chemical
chemical_list: D000924:Anticholesteremic Agents; D001055:Apolipoproteins B; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D000960:Hypolipidemic Agents; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; C009746:etofibrate; D002995:Clofibric Acid; D002784:Cholesterol