title: High density lipoprotein is an inappropriate substrate for hepatic lipase in postmenopausal women.
abstract: BACKGROUND
  HDL antiatherogenic effects would not only depend on its concentration but also on its biological quality. Hepatic lipase (HL) action on HDL acts in one of the last steps of reverse cholesterol transport. Cardiovascular risk increases after menopause, however HDL does not decrease even when HL is increased. We evaluated HDL capacity as a substrate of HL in healthy postmenopausal women (PMW).
  
  
  METHODS
  We studied 20 PMW (51-60 y) and 20 premenopausal (PreMW) (26-40 y). In fasting serum, lipid-lipoprotein profile and HDL composition were assessed. Optimal assay conditions for HDL/HL ex vivo incubation were established. Increasing HDL-triglyceride concentrations (0.015 to 0.20 mmol/l) were incubated with post-heparin plasma obtained from a single healthy donor as a source of HL. Free fatty acids were measured and kinetic parameters calculated: K(m)(app), inverse to enzyme affinity, and V(max).
  
  
  RESULTS
  HDL composition in PMW exhibits triglyceride enrichment (p<0.001). Kinetic analysis revealed higher K(m)(app) in PMW [130 (40-380) vs 45 (20-91) mmol/l, p<0.0001)] correlating directly with HDL-triglycerides (r=0.7, p=0.0001). Catalytic efficiency, V(max)/K(m)(app) was reduced when compared to controls (p=0.0001).
  
  
  CONCLUSIONS
  Triglyceride-enriched HDL from PMW constitutes a poor substrate for HL suggesting that this particle may not exert efficiently its antiatherogenic function, regardless of plasma concentration.
authors.affiliation: Laboratory of Lipids and Lipoproteins, Department of Clinical Biochemistry, Faculty of Pharmacy and Biochemistry, INFIBIOC, University of Buenos Aires, Argentina. vzago@ffyb.uba.ar
authors.forename: Valeria
authors.initials: V
authors.lastname: Zago
authors.forename: Verónica
authors.initials: V
authors.lastname: Miksztowicz
authors.forename: Leonardo
authors.initials: L
authors.lastname: Cacciagiú
authors.forename: Francisco
authors.initials: F
authors.lastname: Basilio
authors.forename: Gabriela
authors.initials: G
authors.lastname: Berg
authors.forename: Laura
authors.initials: L
authors.lastname: Schreier
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D007700:Kinetics; D008049:Lipase / Q000097:blood* / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000097:blood* / Q000302:isolation & purification; D008875:Middle Aged; D017698:Postmenopause / Q000097:blood*; D014280:Triglycerides / Q000097:blood
chemical_list: C504173:LIPC protein, human; D008075:Lipoproteins, HDL; D014280:Triglycerides; D008049:Lipase