Plasma cholesteryl ester transfer, but not cholesterol esterification, is related to lipoprotein-associated phospholipase A2: possible contribution to an atherogenic lipoprotein profile

J Clin Endocrinol Metab. 2011 Apr;96(4):1077-84. doi: 10.1210/jc.2010-2139. Epub 2011 Jan 20.

Abstract

Context: Plasma lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) predicts incident cardiovascular disease and is associated preferentially with negatively charged apolipoprotein B-containing lipoproteins. The plasma cholesteryl ester transfer (CET) process, which contributes to low high-density lipoprotein cholesterol and small, dense low-density lipoproteins, is affected by the composition and concentration of apolipoprotein B-containing cholesteryl ester acceptor lipoproteins.

Objective: We tested relationships of CET with Lp-PLA(2) in subjects with and without metabolic syndrome (MetS).

Design and setting: In 68 subjects with MetS and 74 subjects without MetS, plasma Lp-PLA(2) mass, cholesterol esterification (EST), lecithin:cholesterol acyltransferase (LCAT) activity level, CET, CET protein (CETP) mass, and lipoproteins were measured.

Results: EST, LCAT activity, CET (P < 0.001 for all), and CETP (P = 0.030) were increased, and Lp-PLA(2) was decreased (P = 0.043) in MetS. CET was correlated positively with Lp-PLA(2) in subjects with and without MetS (P < 0.05 for both). EST and LCAT activity were unrelated to Lp-PLA(2), despite a positive correlation between EST and CET (P < 0.001). After controlling for age, sex, and diabetes status, CET was determined by Lp-PLA(2) in the whole group (β = 0.245; P < 0.001), and in subjects with (β = 0.304; P = 0.001) and without MetS (β = 0.244; P = 0.006) separately, independently of triglycerides and CETP.

Conclusions: Plasma CET is related to Lp-PLA(2) in subjects with and without MetS. The process of CET, but not EST, may be influenced by Lp-PLA(2). These findings provide a rationale to evaluate whether maneuvers that inhibit Lp-PLA(2) will reduce CET, and vice versa to document effects of CETP inhibition on Lp-PLA(2).

MeSH terms

  • 1-Alkyl-2-acetylglycerophosphocholine Esterase / metabolism
  • 1-Alkyl-2-acetylglycerophosphocholine Esterase / physiology*
  • Aged
  • Atherosclerosis / blood
  • Atherosclerosis / metabolism*
  • Case-Control Studies
  • Cholesterol / blood
  • Cholesterol / metabolism*
  • Cholesterol Ester Transfer Proteins / metabolism*
  • Cholesterol Esters / blood*
  • Cholesterol Esters / metabolism
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / metabolism
  • Esterification / physiology
  • Female
  • Humans
  • Linear Models
  • Lipoproteins / blood
  • Lipoproteins / metabolism*
  • Male
  • Metabolic Syndrome / blood
  • Metabolic Syndrome / complications
  • Metabolic Syndrome / metabolism
  • Metabolome / physiology
  • Middle Aged
  • Triglycerides / blood
  • Triglycerides / metabolism

Substances

  • Cholesterol Ester Transfer Proteins
  • Cholesterol Esters
  • Lipoproteins
  • Triglycerides
  • Cholesterol
  • 1-Alkyl-2-acetylglycerophosphocholine Esterase