title: Transfer of lipids to high-density lipoprotein (HDL) is altered in patients with familial hypercholesterolemia.
abstract: OBJECTIVE
  In familial hypercholesterolemia (FH), the metabolism and anti-atherogenic functions of HDL can be affected by the continuous interactions with excess LDL amounts. Here, lipid transfers to HDL, an important step for HDL intravascular metabolism and for HDL role in reverse cholesterol transport (RCT) were investigated in FH patients.
  
  
  METHODS
  Seventy-one FH patients (39 ± 15 years, LDL-cholesterol=274 ± 101; HDL-cholesterol=50 ± 14 mg/dl) and 66 normolipidemic subjects (NL) (38 ± 11 years, LDL-cholesterol=105 ± 27; HDL-cholesterol=52 ± 12 mg/dl) were studied. In vitro, lipid transfers were evaluated by incubation of plasma samples (37°C, 1h) with a donor lipid nanoemulsion labeled with 3H-triglycerides (TG) and 14C-unesterified cholesterol (UC) or with 3H-cholesteryl ester (EC) and 14C-phospholipids (PL). Radioactivity was counted at the HDL fraction after chemical precipitation of apolipoprotein (apo) B-containing lipoproteins and the nanoemulsion. Data are % of total radioactivity measured in the HDL fraction.
  
  
  RESULTS
  Transfer of UC to HDL was lower in FH than in NL (5.6 ± 2.1 vs 6.7 ± 2.0%, p=0.0005) whereas TG (5.5 ± 3.1 vs 3.7 ± 0.9%, p=0.018) and PL (20.9 ± 4.6 vs 18.2 ± 3.7 %, p=0.023) transfers were higher in FH. EC transfer was equal. By multivariate analysis, transfers of all four lipids correlated with HDL-cholesterol and with apo A-I.
  
  
  CONCLUSIONS
  FH elicited marked changes in three of the four tested lipid transfers to HDL. The entry of UC into HDL for subsequent esterification is an important driving force for RCT and reduction of UC transfer to HDL was previously associated to precocious coronary heart disease. Therefore, in FH, HDL functions can be lessened, which can also contribute to atherogenesis.
authors.affiliation: Lipid Clinic, Heart Institute (InCor) of the Medical School Hospital, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Lilton R C
authors.initials: LR
authors.lastname: Martinez
authors.forename: Raul D
authors.initials: RD
authors.lastname: Santos
authors.forename: Márcio H
authors.initials: MH
authors.lastname: Miname
authors.forename: Débora F
authors.initials: DF
authors.lastname: Deus
authors.forename: Emerson S
authors.initials: ES
authors.lastname: Lima
authors.forename: Raul C
authors.initials: RC
authors.lastname: Maranhão
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001055:Apolipoproteins B / Q000378:metabolism; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism; D005260:Female; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000235:genetics / Q000378:metabolism*; D050356:Lipid Metabolism / Q000235:genetics*; D008075:Lipoproteins, HDL / Q000235:genetics / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010743:Phospholipids / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D055815:Young Adult
chemical_list: D001055:Apolipoproteins B; D002788:Cholesterol Esters; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D010743:Phospholipids; D014280:Triglycerides; D002784:Cholesterol
keywords: CE; CHD; Cholesterol; Coronary heart disease; FH; HDL metabolism; HDL-C; LCAT; LDL-C; Lipid transfer; Lp(a); Nanoparticle; PL; TC; TG; UC; apo; apolipoprotein; cholesteryl esters; coronary heart disease; familial hypercholesterolemia; high-density lipoprotein-cholesterol; lecithin-cholesterol-acyl-transferase; lipoprotein (a); low-density lipoprotein-cholesterol; phospholipids; total cholesterol; triglycerides; unesterified cholesterol.