Microsomal enzyme inducers raise plasma high-density lipoprotein cholesterol levels in healthy control subjects but not in patients with primary hypoalphalipoproteinemia.
In this study we compared the ability of phenytoin, a microsomal enzyme inducer, to raise plasma high-density lipoprotein (HDL) levels in normolipidemic subjects and patients with primary hypoalphalipoproteinemia. In healthy control subjects, phenytoin caused a dose-dependent increase of plasma HDL, HDL2, and HDL3 cholesterol levels, up to 40% to 50%. Minor changes were recorded in the plasma concentrations of apolipoprotein (apo) A-I and apo A-II; the plasma level of the cholesteryl ester transfer protein (CETP) decreased by 42%. In contrast, none of the patients with hypoalphalipoproteinemia had changes in plasma HDL, HDL2, or HDL3 cholesterol, apo A-I, apo A-II, or CETP levels. These findings indicate that microsomal enzyme inducers are unsuitable to increase plasma HDL levels in high-risk patients with primary hypoalphalipoproteinemia, and they disclose a new mechanism, that is, decreased CETP-mediated transfer of cholesterol out of HDL, for the HDL-raising effect of microsomal enzyme inducers in healthy individuals.
Franceschini
G
G
Center E. Grossi Paoletti, Institute of Pharmacological Sciences, University of Milano, Italy.
Werba
J P
JP
D'Acquarica
A L
AL
Gianfranceschi
G
G
Michelagnoli
S
S
Sirtori
C R
CR
D000368:Aged; D000704:Analysis of Variance; D001053:Apolipoproteins / Q000097:blood; D002352:Carrier Proteins / Q000097:blood; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood*; D004790:Enzyme Induction / Q000502:physiology*; D006023:Glycoproteins; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D008875:Middle Aged; D010672:Phenytoin / Q000494:pharmacology; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000097:blood; D012016:Reference Values; D013631:Tangier Disease / Q000097:blood* / Q000201:enzymology; D014280:Triglycerides / Q000097:blood
D001053:Apolipoproteins; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters; D008076:Cholesterol, HDL; D006023:Glycoproteins; D008055:Lipids; D014280:Triglycerides; D010672:Phenytoin; D007862:Phosphatidylcholine-Sterol O-Acyltransferase