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

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.

• Authors: Shoudong Guo, Hua Tian, Rongrong Dong, Nana Yang, Ying Zhang, Shutong Yao, Yongjun Li, Yawei Zhou, Yanhong Si, Shucun Qin
• Journal: Atherosclerosis (Atherosclerosis) Vol. 251 Pg. 183-191 (08 2016) ISSN: 1879-1484 [Electronic] Ireland
• PMID: 27344369 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Chemical References

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

Topics

• 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)