title: Familial hypercholesterolaemia: cholesterol efflux and coronary disease.
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.
  
  
  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.
authors.affiliation: Department of Internal Medicine, Section of Pharmacology, Vascular and Metabolic Diseases, Cardiovascular Research School COEUR, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Jorie
authors.identifier: http://orcid.org/0000-0003-0674-7765
authors.initials: J
authors.lastname: Versmissen
authors.affiliation: Department of Internal Medicine, Section of Pharmacology, Vascular and Metabolic Diseases, Cardiovascular Research School COEUR, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Ranitha
authors.initials: R
authors.lastname: Vongpromek
authors.affiliation: Department of Internal Medicine, Section of Pharmacology, Vascular and Metabolic Diseases, Cardiovascular Research School COEUR, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Reyhana
authors.initials: R
authors.lastname: Yahya
authors.affiliation: Department of Internal Medicine, Section of Pharmacology, Vascular and Metabolic Diseases, Cardiovascular Research School COEUR, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Jeroen B
authors.initials: JB
authors.lastname: van der Net
authors.affiliation: Department of Internal Medicine, Section of Pharmacology, Vascular and Metabolic Diseases, Cardiovascular Research School COEUR, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Leonie
authors.initials: L
authors.lastname: van Vark-van der Zee
authors.affiliation: Department of Internal Medicine, Section of Pharmacology, Vascular and Metabolic Diseases, Cardiovascular Research School COEUR, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Jeannette
authors.initials: J
authors.lastname: Blommesteijn-Touw
authors.affiliation: Department of Internal Medicine, Section of Pharmacology, Vascular and Metabolic Diseases, Cardiovascular Research School COEUR, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Darcos
authors.initials: D
authors.lastname: Wattimena
authors.affiliation: Department of Internal Medicine, Section of Pharmacology, Vascular and Metabolic Diseases, Cardiovascular Research School COEUR, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Trinet
authors.initials: T
authors.lastname: Rietveld
authors.affiliation: Cardiovascular Research Institute, University of California, San Francisco, CA, USA.|Department of Physiological Nursing, University of California, San Francisco, CA, USA.
authors.forename: Clive R
authors.initials: CR
authors.lastname: Pullinger
authors.affiliation: Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Christina
authors.initials: C
authors.lastname: Christoffersen
authors.affiliation: Wallenberg Laboratory, Department of Laboratory Medicine, Skån University Hospital, Malmö, Sweden.
authors.forename: Björn
authors.initials: B
authors.lastname: Dahlbäck
authors.affiliation: Cardiovascular Research Institute, University of California, San Francisco, CA, USA.|Department of Medicine, University of California, San Francisco, CA, USA.|Department of Biochemistry and Biophysics, University of California, San Francisco, CA, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Kane
authors.affiliation: Department of Internal Medicine, Section of Pharmacology, Vascular and Metabolic Diseases, Cardiovascular Research School COEUR, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Monique
authors.initials: M
authors.lastname: Mulder
authors.affiliation: Department of Internal Medicine, Section of Pharmacology, Vascular and Metabolic Diseases, Cardiovascular Research School COEUR, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Eric J G
authors.initials: EJ
authors.lastname: Sijbrands
mesh_terms: D000328:Adult; D000368:Aged; D016632:Apolipoprotein A-I / Q000378:metabolism; D016633:Apolipoprotein A-II / Q000378:metabolism; D001053:Apolipoproteins / Q000378:metabolism*; D000075243:Apolipoproteins M; D016022:Case-Control Studies; D002784:Cholesterol / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000378:metabolism*; D003327:Coronary Disease / Q000378:metabolism*; D006579:Heterozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000378:metabolism*; D054834:Lipocalins / Q000378:metabolism*; D008246:Lysophospholipids / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000378:metabolism; D065840:Protective Factors; D035781:Siblings; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D055815:Young Adult
chemical_list: C400523:APOM protein, human; D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D001053:Apolipoproteins; D000075243:Apolipoproteins M; D008076:Cholesterol, HDL; D054834:Lipocalins; D008246:Lysophospholipids; D014280:Triglycerides; C060506:sphingosine 1-phosphate; D002784:Cholesterol; D013110:Sphingosine
keywords: Apolipoprotein M; cholesterol efflux; familial hypercholesterolaemia; high-density lipoprotein; sphingolipids; sphingosine-phosphate