The antiatherogenic function of HDL is impaired in hyperhomocysteinemic subjects

Kirsten B Holven1, Pål Aukrust, Kjetil Retterstøl

  • 1Institute for Basic Medical Sciences, Department of Nutrition, University of Oslo, Blindern, 0316 Oslo, Norway. kirsten.holven@medisin.uio.no

The Journal of Nutrition
|October 22, 2008
PubMed

Insights

High homocysteine levels impair high-density lipoprotein (HDL) function, reducing its ability to remove cholesterol and fight inflammation. This dysfunction in HDL may explain increased cardiovascular disease risk in hyperhomocysteinemic individuals.

Area of Science:

  • Cardiovascular Science
  • Metabolic Disorders
  • Lipid Metabolism

Background:

  • High plasma homocysteine is linked to cardiovascular disease risk.
  • Plasma high-density lipoprotein (HDL) concentration is inversely correlated with cardiovascular disorders.
  • Dysfunctional HDL may contribute to cardiovascular events in hyperhomocysteinemic individuals.

Purpose of the Study:

  • To investigate the functionality of HDL in hyperhomocysteinemic subjects.
  • To determine if serum from hyperhomocysteinemic individuals impairs cholesterol efflux and inflammatory mediator release.
  • To assess the antiatherogenic activity of HDL in relation to homocysteine levels.

Main Methods:

  • Serum analysis from hyperhomocysteinemic (n=10) and control (n=10) subjects.
  • Assessed serum's ability to induce cholesterol efflux from macrophages.
  • Evaluated serum's effect on inflammatory mediator release from endothelial cells.
  • Measured paraoxonase activity in serum.

Main Results:

  • Serum from hyperhomocysteinemic subjects showed impaired cholesterol efflux.
  • HDL from these subjects had reduced anti-inflammatory effects on endothelial cells.
  • Paraoxonase activity was significantly reduced in hyperhomocysteinemic individuals.
  • Attenuated suppression of interleukin-6 and growth-related oncogene-alpha release was observed.

Conclusions:

  • Hyperhomocysteinemic individuals exhibit dysfunctional HDL particles.
  • Dysfunctional HDL has attenuated antiatherogenic activity.
  • This HDL dysfunction offers a potential explanation for increased cardiovascular risk in hyperhomocysteinemia.

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