High-level expression of ABCG5 and ABCG8 attenuates diet-induced hypercholesterolemia and atherosclerosis in Ldlr-/- mice

Kenneth R. Wilund, Liqing Yu, Fang Xu, Helen H. Hobbs, Jonathan C. Cohen

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Transgenic mice expressing human ABCG5 (G5) and ABCG8 (G8) have decreased fractional absorption and increased biliary secretion of cholesterol, but their plasma cholesterol levels are unchanged (males) or modestly reduced (females). To determine whether increased expression of G5 and G8 can ameliorate hypercholesterolemia in mice lacking LDL receptors (LDLRs), we examined the effects of G5G8 transgene expression on cholesterol metabolism and atherosclerosis in Ldlr-/- mice. In chow-fed Ldlr-/- mice, the G5G8 transgene reduced fractional absorption of dietary cholesterol by 50% and increased biliary cholesterol levels by 60% but did not affect plasma cholesterol levels. On a Western diet (21% fat, 0.2% cholesterol), G5G8 Tg; Ldlr-/- mice had a 30% reduction in the level of hepatic cholesterol and 45% lower plasma cholesterol levels than the Ldlr -/- mice. After 6 months on the Western diet, the atherosclerotic lesion area in the aortic root and arch was ∼70% lower in the G5G8 Tg;Ldlr-/- than in the Ldlr-/- mice and was correlated with the plasma cholesterol levels. These results demonstrate that increased expression of G5 and G8 attenuates diet-induced hypercholesterolemia in Ldlr-/- mice, resulting in a significant reduction in plasma levels of cholesterol and aortic atherosclerotic lesion area.

Original languageEnglish (US)
Pages (from-to)1429-1436
Number of pages8
JournalJournal of Lipid Research
Volume45
Issue number8
DOIs
StatePublished - Aug 2004

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Nutrition
Hypercholesterolemia
Atherosclerosis
Cholesterol
Diet
Plasmas
Transgenes
Dietary Cholesterol
LDL Receptors
Arches
Thoracic Aorta
Metabolism
Transgenic Mice
Fats
Liver

Keywords

  • Cholesterol absorption
  • Cholesterol secretion
  • Plant sterol

ASJC Scopus subject areas

  • Endocrinology

Cite this

High-level expression of ABCG5 and ABCG8 attenuates diet-induced hypercholesterolemia and atherosclerosis in Ldlr-/- mice. / Wilund, Kenneth R.; Yu, Liqing; Xu, Fang; Hobbs, Helen H.; Cohen, Jonathan C.

In: Journal of Lipid Research, Vol. 45, No. 8, 08.2004, p. 1429-1436.

Research output: Contribution to journalArticle

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