Familial hypercholesterolaemia: cholesterol efflux and coronary disease

Eur J Clin Invest. 2016 Jul;46(7):643-50. doi: 10.1111/eci.12643. Epub 2016 Jun 20.

Abstract

Background: Coronary heart disease (CHD) risk inversely associates with levels of high-density lipoprotein cholesterol (HDL-C). The protective effect of HDL is thought to depend on its functionality, such as its ability to induce cholesterol efflux.

Materials and methods: We compared plasma cholesterol efflux capacity between male familial hypercholesterolaemia (FH) patients with and without CHD relative to their non-FH brothers, and examined HDL constituents including sphingosine-1-phosphate (S1P) and its carrier apolipoprotein M (apoM).

Results: Seven FH patients were asymptomatic and six had experienced a cardiac event at a mean age of 39 years. Compared to their non-FH brothers, cholesterol efflux from macrophages to plasma from the FH patients without CHD was 16 ± 22% (mean ± SD) higher and to plasma from the FH patients with CHD was 7 ± 8% lower (P = 0·03, CHD vs. non-CHD). Compared to their non-FH brothers, FH patients without CHD displayed significantly higher levels of HDL-cholesterol, HDL-S1P and apoM, while FH patients with CHD displayed lower levels than their non-FH brothers.

Conclusions: A higher plasma cholesterol efflux capacity and higher S1P and apoM content of HDL in asymptomatic FH patients may play a role in their apparent protection from premature CHD.

Keywords: Apolipoprotein M; cholesterol efflux; familial hypercholesterolaemia; high-density lipoprotein; sphingolipids; sphingosine-phosphate.

MeSH terms

  • Adult
  • Aged
  • Apolipoprotein A-I / metabolism
  • Apolipoprotein A-II / metabolism
  • Apolipoproteins / metabolism*
  • Apolipoproteins M
  • Case-Control Studies
  • Cholesterol / metabolism*
  • Cholesterol, HDL / metabolism*
  • Coronary Disease / metabolism*
  • Heterozygote
  • Humans
  • Hyperlipoproteinemia Type II / metabolism*
  • Lipocalins / metabolism*
  • Lysophospholipids / metabolism*
  • Macrophages / metabolism*
  • Male
  • Middle Aged
  • Plasma / metabolism
  • Protective Factors
  • Siblings
  • Sphingosine / analogs & derivatives*
  • Sphingosine / metabolism
  • Triglycerides / metabolism
  • Young Adult

Substances

  • APOM protein, human
  • Apolipoprotein A-I
  • Apolipoprotein A-II
  • Apolipoproteins
  • Apolipoproteins M
  • Cholesterol, HDL
  • Lipocalins
  • Lysophospholipids
  • Triglycerides
  • sphingosine 1-phosphate
  • Cholesterol
  • Sphingosine