title: Changes in high-density lipoprotein subfraction distribution and increased cholesteryl ester transfer after probucol.
abstract: The effects of probucol (500 mg twice daily) on high-density lipoprotein (HDL) subfractions and cholesteryl ester transfer from HDL to lower density lipoproteins were tested in a series of patients with Type II hypercholesterolemia. In this placebo-controlled crossover trial, patients received probucol or placebo for 8 weeks, then switched to the other agent for another 8 weeks. Probucol significantly lowered total, low-density lipoprotein and HDL cholesterol levels. HDL subfractions, separated by rate zonal ultracentrifugation, showed a dramatic reduction in HDL2, whereas changes in HDL3 were not significant. Both subfractions eluted at a characteristically lower volume, indicating a reduced flotation rate. These findings were confirmed by gradient gel electrophoretic separation, which showed a typical reduction or disappearance of HDL2b particles and the prevalence of particles in the HDL3a-HDL3b electrophoretic range in almost all patients. After treatment, cholesteryl ester transfer from HDL to lower density lipoproteins was significantly increased in all patients. These data suggest that probucol may accelerate HDL particle conversion, leading to improvement in reverse cholesterol transport from the periphery to the liver, through HDL and very low density lipoprotein.
authors.affiliation: E. Grossi Paoletti Center, Institute of Pharmacological Sciences, Milan, Italy.
authors.forename: C R
authors.initials: CR
authors.lastname: Sirtori
authors.forename: M
authors.initials: M
authors.lastname: Sirtori
authors.forename: L
authors.initials: L
authors.lastname: Calabresi
authors.forename: G
authors.initials: G
authors.lastname: Franceschini
mesh_terms: D002352:Carrier Proteins / Q000097:blood*; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters / Q000097:blood*; D002986:Clinical Trials as Topic; D006023:Glycoproteins; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000188:drug therapy; D008075:Lipoproteins, HDL / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood; D010636:Phenols / Q000627:therapeutic use*; D010919:Placebos; D011341:Probucol / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters; D006023:Glycoproteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D010636:Phenols; D010919:Placebos; D011341:Probucol