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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.
AuthorsXavier Pillois, Thomas Gautier, Benjamin Bouillet, Jean-Paul Pais de Barros, Aline Jeannin, Bruno Vergès, Jacques Bonnet, Laurent Lagrost
JournalJournal of lipid research (J Lipid Res) Vol. 53 Issue 6 Pg. 1200-9 (Jun 2012) ISSN: 1539-7262 [Electronic] United States
PMID22474067 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Apolipoprotein C-I
  • Cholesterol Ester Transfer Proteins
  • Lipoproteins, HDL
  • Lipoproteins, LDL
  • Cholesterol
Topics
  • Apolipoprotein C-I (blood, metabolism)
  • Case-Control Studies
  • Cholesterol (blood, metabolism)
  • Cholesterol Ester Transfer Proteins (antagonists & inhibitors, blood)
  • Coronary Artery Disease (complications)
  • Coronary Stenosis (complications)
  • Dyslipidemias (blood, complications, metabolism)
  • Female
  • Humans
  • Lipoproteins, HDL (blood)
  • Lipoproteins, LDL (blood)
  • Male
  • Middle Aged

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