High density lipoprotein is an inappropriate substrate for hepatic lipase in postmenopausal women

Valeria Zago1, Verónica Miksztowicz, Leonardo Cacciagiú

  • 1Laboratory of Lipids and Lipoproteins, Department of Clinical Biochemistry, Faculty of Pharmacy and Biochemistry, INFIBIOC, University of Buenos Aires, Argentina. vzago@ffyb.uba.ar

Insights

Postmenopausal women have triglyceride-enriched HDL, making it a poor substrate for hepatic lipase (HL). This suggests reduced antiatherogenic function despite normal HDL levels, impacting cardiovascular risk.

Area of Science:

  • Lipid metabolism
  • Cardiovascular disease research
  • Menopause studies

Background:

  • High-density lipoprotein (HDL) plays a crucial role in antiatherogenic effects, influenced by both concentration and quality.
  • Hepatic lipase (HL) modifies HDL during reverse cholesterol transport.
  • Cardiovascular risk elevates post-menopause, yet HDL levels remain stable despite increased HL.

Purpose of the Study:

  • To evaluate HDL's capacity as a substrate for HL in healthy postmenopausal women (PMW).
  • To compare HDL substrate quality between PMW and premenopausal women (PreMW).

Main Methods:

  • Studied 20 PMW (51-60 years) and 20 PreMW (26-40 years).
  • Assessed fasting serum lipid-lipoprotein profile and HDL composition.
  • Incubated increasing HDL-triglyceride concentrations with HL from post-heparin plasma and measured kinetic parameters (Km(app), Vmax).

Main Results:

  • HDL from PMW showed significant triglyceride enrichment compared to PreMW (p<0.001).
  • Kinetic analysis revealed higher apparent Michaelis constant (Km(app)) in PMW (p<0.0001), directly correlating with HDL triglycerides.
  • Catalytic efficiency (Vmax/Km(app)) was reduced in PMW compared to controls (p=0.0001).

Conclusions:

  • Triglyceride-rich HDL in PMW is a poor substrate for HL.
  • This impaired substrate quality suggests that HDL may not effectively perform its antiatherogenic function in PMW.
  • Reduced HDL quality, not just concentration, may contribute to increased cardiovascular risk post-menopause.
Abstract

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