Increased cholesterol efflux capacity in metabolic syndrome: Relation with qualitative alterations in HDL and LCAT

Atherosclerosis. 2015 Sep;242(1):236-42. doi: 10.1016/j.atherosclerosis.2015.07.019. Epub 2015 Jul 10.

Abstract

Background: Metabolic syndrome (MetS) is associated with changes in HDL levels, composition and sub-fraction profile. Whether these alterations affect HDL anti-atherogenic function, specifically measured as its capacity to perform cholesterol efflux, is not yet clearly known.

Objective: To evaluate the relation between serum cholesterol efflux capacity and the changes in HDL composition and sub-fraction profile in MetS.

Methods: In 35 non-treated MetS patients and 15 healthy controls, HDL mediated cholesterol efflux was measured as the ability of apoB-depleted serum to accept cholesterol from cholesterol-loaded BHK cells expressing either ABCA1 or ABCG1. Additionally we determined: lipid profile, HDL sub-fractions (NMR) and LCAT mass (ELISA). Isolated HDL (δ:1.063-1.210 g/mL) was chemically characterized. Pre-β1-HDL was determined by 2D-electrophoresis in a sub-group of MetS and controls (n = 6 each).

Results: Surprisingly, MetS patients presented higher ABCA1 mediated cholesterol efflux (10.4 ± 1.8 vs. 8.7 ± 0.3%; p = 0.0001), without differences in ABCG1 efflux. In MetS, HDL showed reduction in particle size and number (p < 0.02) and lower large/small HDL ratio (p = 0.05), as well as triglyceride enrichment (p = 0.0001). Pre-β1-HDL was increased in MetS (p = 0.048) and correlated with ABCA1-cholesterol efflux (r = 0.64; p = 0.042). LCAT mass showed a tendency to reduction in MetS (p = 0.08), and inversely correlated with ABCA1-cholesterol efflux (r = -0.51; p = 0.001), independently of obesity and insulin-resistance (β = -0.40, p = 0.034).

Conclusion: This is the first description of ABCA1 mediated cholesterol efflux in MetS. Regardless the reduced HDL-cholesterol, in vitro cholesterol efflux capacity by ABCA1 was enhanced, linked to increased pre-β1-HDL and slightly reduced in LCAT mass that would probably reflect a delay in reverse cholesterol transport occurring in MetS.

Keywords: Cholesterol efflux capacity; HDL; LCAT; Metabolic syndrome; Pre-β1-HDL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter 1 / genetics
  • ATP Binding Cassette Transporter 1 / metabolism
  • ATP Binding Cassette Transporter, Subfamily G, Member 1
  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism
  • Adult
  • Animals
  • Biomarkers / blood
  • Case-Control Studies
  • Cell Line
  • Cholesterol / blood*
  • Cholesterol, HDL / blood*
  • Cricetinae
  • Female
  • High-Density Lipoproteins, Pre-beta / blood
  • Humans
  • Male
  • Metabolic Syndrome / blood*
  • Metabolic Syndrome / diagnosis
  • Metabolic Syndrome / enzymology
  • Metabolic Syndrome / genetics
  • Middle Aged
  • Phosphatidylcholine-Sterol O-Acyltransferase / metabolism*
  • Transfection

Substances

  • ABCA1 protein, human
  • ABCG1 protein, human
  • ATP Binding Cassette Transporter 1
  • ATP Binding Cassette Transporter, Subfamily G, Member 1
  • ATP-Binding Cassette Transporters
  • Biomarkers
  • Cholesterol, HDL
  • High-Density Lipoproteins, Pre-beta
  • Cholesterol
  • Phosphatidylcholine-Sterol O-Acyltransferase