Exogenous supplement of N-acetylneuraminic acid ameliorates atherosclerosis in apolipoprotein E-deficient mice

Atherosclerosis. 2016 Aug:251:183-191. doi: 10.1016/j.atherosclerosis.2016.05.032. Epub 2016 May 19.

Abstract

Background and aims: Previous studies investigating the correlation between plasma sialic acid and the severity of atherosclerosis present conflicting results. In atherosclerosis patients, plasma levels of N-acetylneuraminic acid (NANA) are increased; however, the underlying mechanisms have not yet been clarified. We assume the increased NANA level may be a compensatory mechanism due to oxidative stress and/or inflammation. The aim of this study is to investigate whether supplementation of NANA could attenuate the progression of atherosclerosis.

Methods: Exogenous NANA was used to determine its effect on apolipoprotein E-deficient (apoE(-/-)) mice taking natural quercetin as a positive control. The effect of NANA on lipid lowering, antioxidant activity and anti-inflammation was investigated by methods of molecular biology.

Results: 1) NANA administration decreased 18.9% of the atherosclerotic plaque formation in the aorta and 26.7% of the lipid deposition in the liver of high-fat diet apoE(-/-) mice; 2) notably, NANA treatment reduced 62.6% of the triglyceride by improving lipoprotein lipase activity; 3) NANA lowered 17.5% of the plasma total cholesterol by up-regulating reverse cholesterol transport (RCT)-related protein expression such as ATP-binding cassette transporter (ABC) G1 and ABCG5 in liver or small intestine; 4) NANA administration notably decreased oxidative stress by increasing antioxidant enzymes activity and protein expression of paraoxonase 1 and 2; 5) NANA markedly reduced tumour necrosis factor-α and intercellular adhesion molecule-1 expression in aorta and liver.

Conclusions: NANA exhibited triglyceride lowering, anti-oxidation, and RCT promoting activities, and therefore NANA supplementation may be a new strategy for prevention and treatment of atherosclerosis.

Keywords: Anti-Oxidation; Anti-inflammation; Cardiovascular disease; Quercetin; Reverse cholesterol transport; Sialic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / chemistry
  • Aorta / metabolism
  • Atherosclerosis / drug therapy*
  • Biological Assay
  • Cholesterol / blood
  • Inflammation
  • Intercellular Adhesion Molecule-1 / blood
  • Lipids / blood
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout, ApoE
  • N-Acetylneuraminic Acid / therapeutic use*
  • Oxidative Stress
  • Oxygen / chemistry
  • Quercetin / pharmacology
  • Triglycerides / genetics
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Antioxidants
  • Lipids
  • Triglycerides
  • Tumor Necrosis Factor-alpha
  • Intercellular Adhesion Molecule-1
  • Cholesterol
  • Quercetin
  • N-Acetylneuraminic Acid
  • Oxygen