title: High-density lipoprotein-associated sphingosine-1-phosphate activity in heterozygous familial hypercholesterolaemia.
abstract: BACKGROUND
  Patients with heterozygous familial hypercholesterolaemia (FH) suffer from high plasma cholesterol and an environment of increased oxidative stress. We examined its potential effects on high-density lipoprotein (HDL)-associated sphingosine-1-phosphate (S1P) content (HDL-S1P) and HDL-mediated protection against oxidative stress, both with and without statin treatment.
  
  
  METHODS
  In a case-control study, HDL was isolated from 12 FH patients with and without statin treatment and from 12 healthy controls. The HDL-S1P content and the capacity of HDL to protect cardiomyocytes against oxidative stress in vitro were measured.
  
  
  RESULTS
  HDL-associated S1P was significantly correlated with cell protection, but not with HDL-cholesterol or apolipoprotein AI. The latter did not correlate with HDL-mediated cell protection. Neither the HDL-S1P content nor HDL protective capacity differed between nontreated FH patients and controls. The relative amounts of apolipoprotein AI and apolipoprotein M were similar between controls and FH patients. Statin treatment had no effect on any of these measures.
  
  
  CONCLUSIONS
  The FH environment is not detrimental to HDL-S1P content or HDL-S1P-mediated cell protection. Statin treatment does not modulate HDL function in this regard.
authors.affiliation: Department of internal medicine specialities, Medical Faculty, Geneva University, Geneva, Switzerland.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Frias
authors.affiliation: Unit of Toxicology, University Centre of Legal Medicine, Lausanne-Geneva, Switzerland.
authors.forename: Aurélien
authors.initials: A
authors.lastname: Thomas
authors.affiliation: Department of internal medicine specialities, Medical Faculty, Geneva University, Geneva, Switzerland.
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Brulhart-Meynet
authors.affiliation: Division of Cardiology, Department of Medicine, Karolinska Institutet at Karolinska University Hospital Solna, Stockholm, Sweden.
authors.forename: Oskar
authors.initials: O
authors.lastname: Kövamees
authors.affiliation: Division of Cardiology, Department of Medicine, Karolinska Institutet at Karolinska University Hospital Solna, Stockholm, Sweden.
authors.forename: John
authors.initials: J
authors.lastname: Pernow
authors.affiliation: Metabolism Unit, Department of Endocrinology, Metabolism and Diabetes, Centre for Innovative Medicine, Karolinska Institutet, Stockholm, Sweden.|KI/AZ Integrated CardioMetabolic Centre, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Eriksson
authors.affiliation: Metabolism Unit, Department of Endocrinology, Metabolism and Diabetes, Centre for Innovative Medicine, Karolinska Institutet, Stockholm, Sweden.|KI/AZ Integrated CardioMetabolic Centre, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Bo
authors.initials: B
authors.lastname: Angelin
authors.affiliation: Department of internal medicine specialities, Medical Faculty, Geneva University, Geneva, Switzerland.
authors.forename: Richard W
authors.initials: RW
authors.lastname: James
authors.affiliation: Department of internal medicine specialities, Medical Faculty, Geneva University, Geneva, Switzerland.|Metabolism Unit, Department of Endocrinology, Metabolism and Diabetes, Centre for Innovative Medicine, Karolinska Institutet, Stockholm, Sweden.|KI/AZ Integrated CardioMetabolic Centre, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Jonas W
authors.initials: JW
authors.lastname: Brinck
mesh_terms: D000328:Adult; D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism*; D016022:Case-Control Studies; D002478:Cells, Cultured; D008076:Cholesterol, HDL / Q000378:metabolism; D002853:Chromatography, Liquid; D005260:Female; D006579:Heterozygote; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006938:Hyperlipoproteinemia Type II / Q000188:drug therapy / Q000378:metabolism*; D066298:In Vitro Techniques; D008075:Lipoproteins, HDL / Q000378:metabolism* / Q000494:pharmacology; D008246:Lysophospholipids / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D032383:Myocytes, Cardiac / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism; D053719:Tandem Mass Spectrometry; D055815:Young Adult
chemical_list: D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008075:Lipoproteins, HDL; D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D013110:Sphingosine
keywords: Apolipoprotein M; cardiomyocyte; high-density lipoprotein; oxidative stress; sphingosine-1-phosphate