Concentration-Dependent Effects of N-3 Long-Chain Fatty Acids on Na,K-ATPase Activity in Human Endothelial Cells

Molecules. 2019 Dec 28;25(1):128. doi: 10.3390/molecules25010128.

Abstract

N-3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) seem to prevent endothelial dysfunction, a crucial step in atherogenesis, by modulating the levels of vasoactive molecules and by influencing Na,K-ATPase activity of vascular myocytes. The activity of endothelial Na,K-ATPase controls the ionic homeostasis of the neighboring cells, as well as cell function. However, controversy exists with respect to the vascular protective effect of EPA and DHA. We argue that this dispute might be due to the use of different concentrations of EPA and DHA in different studies. Therefore, this study was designed to define an optimal concentration of EPA and DHA to investigate endothelial function. For this purpose, human endothelial cells were exposed for 24 h to different concentrations of DHA or EPA (0-20 μM) to study membrane fluidity, peroxidation potential and Na,K-ATPase activity. EPA and DHA were linearly incorporated and this incorporation was mirrored by the linear increase of unsaturation index, membrane fluidity, and peroxidation potential. Na,K-ATPase activity peaked at 3.75 μM of EPA and DHA and then gradually decreased. It is noteworthy that DHA effects were always more pronounced than EPA. Concluding, low concentrations of EPA and DHA minimize peroxidation sensitivity and optimize Na,K-ATPase activity.

Keywords: docosahexaenoic acid; eicosapentaenoic acid; endothelium; lipid peroxidation; membrane fluidity; sodium pump.

MeSH terms

  • Atherosclerosis / enzymology*
  • Atherosclerosis / pathology
  • Atherosclerosis / prevention & control
  • Docosahexaenoic Acids / pharmacology*
  • Eicosapentaenoic Acid / analogs & derivatives*
  • Eicosapentaenoic Acid / pharmacology
  • Endothelial Cells / enzymology*
  • Endothelial Cells / pathology
  • Homeostasis / drug effects
  • Humans
  • Membrane Fluidity / drug effects*
  • Sodium-Potassium-Exchanging ATPase

Substances

  • Docosahexaenoic Acids
  • eicosapentaenoic acid ethyl ester
  • Eicosapentaenoic Acid
  • Sodium-Potassium-Exchanging ATPase