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High-Density Lipoprotein Particles, Cell-Cholesterol Efflux, and Coronary Heart Disease Risk

Bela F Asztalos1, Katalin V Horvath1, Ernst J Schaefer1

  • 1From the Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA.

Arteriosclerosis, Thrombosis, and Vascular Biology
|July 14, 2018
PubMed

Insights

Coronary heart disease patients show altered high-density lipoprotein (HDL) function. While preβ-1 HDL levels are higher, their cholesterol efflux capacity is reduced, and large HDL particles have enhanced functionality despite lower concentrations.

Area of Science:

  • Cardiovascular Research
  • Lipid Metabolism
  • Atherosclerosis

Background:

  • High-density lipoprotein (HDL) cholesterol efflux capacity is inversely associated with coronary heart disease (CHD) risk.
  • ATP-binding cassette transporter A1 (ABCA1) is critical for cholesterol efflux to preβ-1 HDL particles.
  • The functional status of HDL particles in CHD patients remains incompletely understood.

Purpose of the Study:

  • To test the hypothesis that CHD patients possess functionally abnormal preβ-1 HDL particles.
  • To investigate the relationship between HDL particle concentration, functionality, and cholesterol efflux capacity in CHD.
  • To assess HDL antioxidative capacity and inflammatory markers in relation to HDL functionality.

Main Methods:

  • A case-control study involving 100 CHD cases and 100 sex-matched controls.
  • Measurement of HDL cholesterol efflux capacity via ABCA1 and scavenger receptor class B type I (SR-BI) pathways.
  • Quantification of HDL antioxidative capacity, apoA-I containing HDL particles, and inflammatory/oxidative stress markers.

Main Results:

  • Significant positive correlations were observed between ABCA1-dependent efflux and preβ-1 HDL levels (R²=0.535).
  • Significant positive correlations were observed between SR-BI-dependent efflux and large HDL (α-1+α-2) particle levels (R²=0.712).
  • CHD cases exhibited higher preβ-1 concentrations (87%) but lower functionality (-31%), and lower large HDL concentrations (-12%) but higher functionality (22%) compared to controls.
  • HDL antioxidative capacity was significantly lower in cases (-16%) with no correlation to HDL particle functionality.

Conclusions:

  • HDL cholesterol efflux capacity is determined by both the concentration and functionality of specific HDL particles.
  • CHD patients display increased concentrations of preβ-1 HDL with impaired functionality.
  • CHD patients also show decreased concentrations of large HDL particles with enhanced functionality.

Keywords:
ATP-binding cassette transportercholesterollipoproteinsmacrophagesoxidative-stress

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