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

Familial hypercholesterolaemia: cholesterol efflux and coronary disease

Jorie Versmissen  1 , Ranitha Vongpromek  1 , Reyhana Yahya  1 , Jeroen B van der Net  1 , Leonie van Vark-van der Zee  1 , Jeannette Blommesteijn-Touw  1 , Darcos Wattimena  1 , Trinet Rietveld  1 , Clive R Pullinger  2   3 , Christina Christoffersen  4 , Björn Dahlbäck  5 , John P Kane  2   6   7 , Monique Mulder  1 , Eric J G Sijbrands  1
Affiliations

Familial hypercholesterolaemia: cholesterol efflux and coronary disease

Jorie Versmissen et al. Eur J Clin Invest. 2016 Jul.

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.

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Figures

Figure 1
Figure 1
Study design. Seven sib‐pairs consisted of one FH and one non‐FH brother, both without CHD. Six pairs consisted of one brother with FH and CHD, the other without FH and CHD. FH, familial hypercholesterolaemia; CHD, coronary heart disease.
Figure 2
Figure 2
Difference in cholesterol efflux from cholesterol‐labelled macrophages to plasma. (a) Individual differences in cholesterol efflux to plasma from an FH patient and his non‐FH brother as a percentage of the efflux to plasma of the non‐FH sib taken as 100%. Some lines (No CHD two, CHD four) almost completely overlap. (b) Percentages difference in cholesterol efflux when compared to the brother without FH. FH, familial hypercholesterolaemia; CHD, coronary heart disease.
Figure 3
Figure 3
Levels of cholesterol (a), S1P in high‐density lipoprotein (HDL) (b) and apoM (c), and apoM in plasma (d). In c, apoM was measured in all separate HDL density fractions that were pooled from all individuals in each group. In d, apoM plasma concentrations were measured in each individual, and values in each familial hypercholesterolaemia patient were connected to his respective brother. Data are expressed as % of an unrelated control pool plasma.
See this image and copyright information in PMC

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