Dietary phytosterol does not accumulate in the arterial wall and prevents atherosclerosis of LDLr-KO mice

Atherosclerosis. 2013 Dec;231(2):442-7. doi: 10.1016/j.atherosclerosis.2013.10.015. Epub 2013 Oct 25.

Abstract

Scope: There have been conflicting reports on the usefulness of phytosterols (PS) in preventing atherosclerosis. We evaluated the effects of dietary PS supplementation in LDLr-KO male mice on the plasma and aorta sterol concentrations and on atherosclerotic lesion development.

Methods and results: Mice were fed a high fat diet (40% of energy) supplemented with or without PS (2% w/w, n = 10). Plasma and arterial wall cholesterol and PS concentrations, lesion area, macrophage infiltration, and mRNA expression from LOX-1, CD36, ABCA1 and ABCG1 in peritoneal macrophages were measured. After 16 weeks, the plasma cholesterol concentration in PS mice was lower than that in the controls (p = 0.02) and in the arterial wall (p = 0.03). Plasma PS concentrations were higher in PS-fed animals than in controls (p < 0.0001); however, the arterial wall PS concentration did not differ between groups. The atherosclerotic lesion area in the PS group (n = 5) was smaller than that in controls (p = 0.0062) and the macrophage area (p = 0.0007). PS correlates negatively with arterial lipid content and macrophage (r = -0.76; p < 0.05). PS supplementation induced lower ABCG1 mRNA expression (p < 0.05).

Conclusions: Despite inducing an increase in PS plasma concentration, PS supplementation is not associated with its accumulation in the arterial wall and prevents atherosclerotic lesion development.

Keywords: Atherosclerosis; Cholesterol absorption; Diet; LDLr-KO mice; Phytosterol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter 1 / metabolism
  • ATP Binding Cassette Transporter, Subfamily G, Member 1
  • ATP-Binding Cassette Transporters / metabolism
  • Absorption
  • Animals
  • Aorta / pathology
  • Arteries / pathology*
  • Atherosclerosis / pathology
  • Atherosclerosis / prevention & control*
  • Body Weight
  • CD36 Antigens / metabolism
  • Cholesterol / metabolism
  • Feeding Behavior
  • Lipids / blood
  • Lipoproteins / metabolism
  • Macrophages / metabolism
  • Macrophages, Peritoneal / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Phytosterols / blood
  • Phytosterols / chemistry*
  • Receptors, LDL / genetics*
  • Scavenger Receptors, Class E / metabolism

Substances

  • ABCA1 protein, mouse
  • ABCG1 protein, mouse
  • ATP Binding Cassette Transporter 1
  • ATP Binding Cassette Transporter, Subfamily G, Member 1
  • ATP-Binding Cassette Transporters
  • CD36 Antigens
  • Lipids
  • Lipoproteins
  • Olr1 protein, mouse
  • Phytosterols
  • Receptors, LDL
  • Scavenger Receptors, Class E
  • Cholesterol