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Influence of HDL particles on cell-cholesterol efflux under various pathological conditions

Bela F Asztalos1,2, Katalin V Horvath3,2, Michael Mehan2

  • 1Cardiovascular Nutrition Laboratory, Human Nutrition Research Center on Aging at Tufts University, Boston, MA bela.asztalos@tufts.edu.

Journal of Lipid Research
|April 20, 2017
PubMed

Insights

High triglyceride levels impact HDL cholesterol efflux capacity by altering both the quantity and function of HDL particles. This suggests that HDL

Area of Science:

  • Cardiovascular Research
  • Lipid Metabolism
  • Atherosclerosis

Background:

  • Low cholesterol efflux capacity (CEC) of high-density lipoprotein (HDL) is a known risk factor for cardiovascular disease (CVD).
  • Understanding the regulation of CEC is crucial for developing targeted therapies.
  • HDL particles play a complex role in cholesterol transport and cardiovascular health.

Purpose of the Study:

  • To investigate the regulation of CEC by examining ABCA1- and SR-BI-dependent cholesterol efflux in relation to HDL particle characteristics.
  • To assess the impact of elevated plasma markers like triglycerides (TG), serum amyloid A (SAA), fibrinogen, myeloperoxidase (MPO), and β-sitosterol on HDL functionality.
  • To differentiate between quantitative (concentration) and qualitative (functional) aspects of HDL in CEC.

Main Methods:

  • Measured ABCA1- and SR-BI-dependent cholesterol efflux in 122 subjects with elevated plasma markers and 146 controls.
  • Assessed HDL anti-oxidative capacity, particle size distribution, lipid profiles, and inflammatory/oxidative stress markers.
  • Correlated cholesterol efflux with HDL particle concentrations (preβ-1 and α-1 + α-2) and plasma marker levels.

Main Results:

  • In controls, strong positive correlations were observed between ABCA1 efflux and small preβ-1 HDL, and SR-BI efflux and large α-1 + α-2 HDL.
  • In high-TG patients, preβ-1 particles showed increased concentration and functionality, while large HDL particles decreased in concentration but increased in functionality.
  • High SAA or MPO levels did not impair HDL particle functionality; however, high β-sitosterol negatively affected HDL anti-oxidative capacity.

Conclusions:

  • CEC is influenced by both the concentration and functional properties of HDL particles.
  • Elevated triglycerides can alter HDL functionality, potentially impacting cardiovascular risk.
  • HDL's role in cholesterol efflux is complex and depends on particle characteristics and specific lipid/inflammatory markers.

Keywords:
adenosine triphosphate binding cassette transporter A1apolipoprotein A-Icardiovascular disease riskpreβ-1scavenger receptor class B type I

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