title: Altered composition of HDL3 in FH subjects causing a HDL subfraction with less atheroprotective function.
abstract: BACKGROUND
  Subjects with familial hypercholesterolemia (FH) are associated with increased risk of premature atherosclerosis and coronary artery disease (CAD). However, onset of clinically manifested CAD varies widely among subjects with heterozygous FH. The purpose of this study was to investigate whether FH subjects with an identical mutation in the low-density lipoprotein (LDL) receptor gene have a high-density lipoprotein (HDL)3 that is characterized by a less atheroprotective functions than that of healthy controls and within subgroups of FH.
  
  
  METHODS
  Twenty-two adults <75 years of age with FH and 17 healthy sex- and age-matched controls were included. HDL3 was isolated and the composition was characterized from each subject, and its ability to suppress tumor necrosis factor(TNF)-alpha stimulated expression of ICAM-1 on HUVEC was investigated. In addition, plasma level of soluble sICAM-1 and VCAM-1 was measured.
  
  
  RESULTS
  Compared to controls, FH subjects had lower content of phospholipids in their HDL3 subfraction and a higher serum ICAM-1 level. No differences in sVCAM-1 were observed. HDL3 isolated from FH with body mass index(BMI)>25 and from FH subjects with premature CAD contained higher content of triglycerides compared to the HDL3 from FH subjects with BMI<25 and without CAD, respectively. Most important, when testing the function of HDL3 in the two FH subgroups characterized by elevated BMI and premature CAD, lower inhibition of ICAM-1 expression on HUVEC was observed.
  
  
  CONCLUSIONS
  The altered composition of HDL3 from FH subjects with BMI>25 and FH subjects with premature CAD may be responsible for a HDL3 subfraction with less protective properties assessed as inhibition of ICAM-1 expression on HUVEC consequently leading to more proatherogenic endothelial surface.
authors.affiliation: Lipid Clinic, Norway.
authors.forename: T R
authors.initials: TR
authors.lastname: Balstad
authors.forename: K B
authors.initials: KB
authors.lastname: Holven
authors.forename: I O
authors.initials: IO
authors.lastname: Ottestad
authors.forename: K
authors.initials: K
authors.lastname: Otterdal
authors.forename: B
authors.initials: B
authors.lastname: Halvorsen
authors.forename: A M
authors.initials: AM
authors.lastname: Myhre
authors.forename: L
authors.initials: L
authors.lastname: Ose
authors.forename: M S
authors.initials: MS
authors.lastname: Nenseter
mesh_terms: D000328:Adult; D001161:Arteriosclerosis / Q000097:blood / Q000517:prevention & control*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood*; D007124:Immunoenzyme Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008075:Lipoproteins, HDL / Q000097:blood*; D053440:Lipoproteins, HDL3; D008297:Male; D008875:Middle Aged; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
chemical_list: D008075:Lipoproteins, HDL; D053440:Lipoproteins, HDL3; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1