Induction of atherosclerosis by low-fat, semisynthetic diets in LDL receptor-deficient C57BL/6J and FVB/NJ mice: comparison of lesions of the aortic root, brachiocephalic artery, and whole aorta (en face measurement)

Arterioscler Thromb Vasc Biol. 2003 Oct 1;23(10):1907-13. doi: 10.1161/01.ATV.0000090126.34881.B1. Epub 2003 Aug 7.

Abstract

Objective: A semisynthetic diet with varying amounts of cholesterol was used to achieve hypercholesterolemia and atherosclerosis in LDL receptor-deficient (LDLR-/-) mice. Atherosclerotic lesions were measured as cross-sectional area at the aortic root and brachiocephalic artery and by en face analysis of aortic lesion area in 209 male and female animals on the C57BL/6J (B6.LDLR-/-) and FVB/NJ (FVB.LDLR-/-) backgrounds.

Methods and results: The semisynthetic diet containing 4.3% fat and 0.00% or 0.02% cholesterol was sufficient to induce hypercholesterolemia (12.6+/-2.4 mmol/L) and atherosclerosis in B6.LDLR-/- mice at the aortic root (98,980+/-37 727 microm2) and brachiocephalic artery (12,039+/-12,750 microm2) but did not produce significant lesions in the aorta measurable by the en face method. Raising dietary cholesterol to 0.15%, 0.30%, or 0.50% more than doubled plasma cholesterol levels (35.9+/-8.5 mmol/L) and resulted in significant en face lesions. It also led to a significant increase in atherosclerotic lesion area at the aortic root (547,753+/-182,151 microm2) and brachiocephalic arteries (125,666+/-59,339 microm2). Although FVB.LDLR-/- mice developed comparable cholesterol levels, they were relatively atherosclerosis resistant and had many-fold smaller lesions.

Conclusions: These results should aid investigations of atherosclerosis in LDLR-/- mice by informing the selection of diet to be used and the location of lesions to be scored.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Analysis of Variance
  • Animals
  • Aorta / pathology*
  • Arteriosclerosis / etiology*
  • Arteriosclerosis / genetics
  • Arteriosclerosis / pathology
  • Brachiocephalic Trunk / pathology*
  • Cholesterol / blood*
  • Cholesterol, Dietary / administration & dosage
  • Diet, Fat-Restricted*
  • Disease Models, Animal
  • Female
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Receptors, LDL / deficiency
  • Receptors, LDL / genetics
  • Species Specificity
  • Triglycerides / blood

Substances

  • Cholesterol, Dietary
  • Receptors, LDL
  • Triglycerides
  • Cholesterol