title: Constitutive inhibition of plasma CETP by apolipoprotein C1 is blunted in dyslipidemic patients with coronary artery disease.
abstract: Plasma cholesteryl ester transfer protein (CETP) promotes the cholesterol enrichment of apoB-containing lipoproteins (VLDL and LDL) at the expense of HDL. Recent studies demonstrated that apoC1 is a potent CETP inhibitor in plasma of healthy, normolipidemic subjects. Our goal was to establish whether the modulation of CETP activity by apoC1 is influenced by dyslipidemia in patients with documented coronary artery disease (CAD). In the total CAD population studied (n = 240), apoC1 levels correlated negatively with CETP activity, independently of apoE-epsilon, CETP-Taq1B, and apoC1-Hpa1 genotypes. In multivariate analysis, the negative relationship was observed only in normolipidemic patients, not in those with hypercholesterolemia, hypertriglyceridemia, or combined hyperlipidemia. In the normolipidemic subjects, apoC1 levels were positively associated with higher HDL- to LDL-cholesterol ratio (r = 0.359, P < 0.001). It is concluded that apoC1 as a CETP inhibitor no longer operates on cholesterol redistribution in high-risk patients with dyslipidemia, probably due to increasing amounts of VLDL-bound apoC1, which is inactive as a CETP inhibitor. Patients with dyslipidemia could experience major benefits from treatment with pharmacological CETP inhibitors, which might compensate for blunted endogenous inhibition.
authors.affiliation: University Victor Segalen of Bordeaux II-INSERM Research Center UMR828, Bordeaux,  France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Pillois
authors.forename: Thomas
authors.initials: T
authors.lastname: Gautier
authors.forename: Benjamin
authors.initials: B
authors.lastname: Bouillet
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Pais de Barros
authors.forename: Aline
authors.initials: A
authors.lastname: Jeannin
authors.forename: Bruno
authors.initials: B
authors.lastname: Vergès
authors.forename: Jacques
authors.initials: J
authors.lastname: Bonnet
authors.forename: Laurent
authors.initials: L
authors.lastname: Lagrost
mesh_terms: D053302:Apolipoprotein C-I / Q000097:blood / Q000378:metabolism*; D016022:Case-Control Studies; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors* / Q000097:blood*; D003324:Coronary Artery Disease / Q000150:complications*; D023921:Coronary Stenosis / Q000150:complications; D050171:Dyslipidemias / Q000097:blood / Q000150:complications* / Q000378:metabolism*; D005260:Female; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged
chemical_list: D053302:Apolipoprotein C-I; D053480:Cholesterol Ester Transfer Proteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D002784:Cholesterol