Chitosan Oligosaccharides Attenuate Atherosclerosis and Decrease Non-HDL in ApoE-/- Mice

J Atheroscler Thromb. 2015;22(9):926-41. doi: 10.5551/jat.22939. Epub 2015 Apr 3.

Abstract

Aim: Chitosan-oligosaccharides (COS) treatment showed lipid lowering effects in rats and reverse cholesterol transport (RCT) promotion in mice, suggested that COS might be a potential atheroprotective material. In this study, we investigated the effects of COS treatment on atherosclerosis (AS) in apolipoprotein E deficient mice (apoE-/-).

Methods: After feeding high fat (HF) diet for 12 weeks with the gastric gavages administration of COS or vehicle, respectively, the mice were sacrificed for the assessment of atherosclerosis, plaque stability, and the mechanism investigation.

Results: Cholesterol and TG in non-high density lipoprotein (non-HDL) fractions were reduced dramatically in COS groups. The COS treatment decreased the lesion areas of aortic enface, plaque areas in aortic root, and increased plaque stability in apoE-/-. Furthermore, the COS treatment significantly enhanced the expression of liver low density lipoprotein receptor (LDL-R), scavenger receptor BI (SR-BI) as well as the expression of macrophage SR-BI and ATP binding cassette transporter A1(ABCA1). We also found that the COS treatment did not affect the plasma lipid level in LDL-R deficient mice and cholesterol absorption in wild type mice.

Conclusions: COS treatment attenuated AS and decreased plasma non-HDL level in apoE-/-, and the potential mechanism might be involved with enhanced expression of hepatic LDL-R and SR-BI, and macrophage ABCA1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter 1 / metabolism
  • ATP Binding Cassette Transporter, Subfamily G, Member 5
  • ATP-Binding Cassette Transporters / metabolism
  • Animals
  • Aorta / pathology
  • Apolipoproteins E / genetics
  • Atherosclerosis / metabolism*
  • Atherosclerosis / therapy*
  • Biological Transport
  • Cell Line
  • Chitosan / chemistry
  • Chitosan / therapeutic use*
  • Cholesterol / blood
  • Cholesterol / genetics*
  • Cholesterol, HDL / blood
  • Cholesterol, HDL / genetics*
  • Disease Models, Animal
  • Hep G2 Cells
  • Humans
  • Lipids / blood
  • Lipoproteins / metabolism
  • Macrophages / metabolism
  • Male
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • Mice, Knockout
  • Oligosaccharides / chemistry
  • Oligosaccharides / therapeutic use*
  • Receptors, LDL / metabolism
  • Scavenger Receptors, Class B / metabolism
  • Triglycerides / blood

Substances

  • ABCA1 protein, mouse
  • ABCG5 protein, mouse
  • ATP Binding Cassette Transporter 1
  • ATP Binding Cassette Transporter, Subfamily G, Member 5
  • ATP-Binding Cassette Transporters
  • Apolipoproteins E
  • Cholesterol, HDL
  • Lipids
  • Lipoproteins
  • Oligosaccharides
  • Receptors, LDL
  • Scarb1 protein, mouse
  • Scavenger Receptors, Class B
  • Triglycerides
  • Chitosan
  • Cholesterol
  • Matrix Metalloproteinase 9
  • Mmp9 protein, mouse