Defective lipoprotein receptors and atherosclerosis. Lessons from an animal counterpart of familial hypercholesterolemia

J. L. Goldstein, T. Kita, M. S. Brown

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Abstract

A new animal model for endogenous hypercholesterolemia has recently become available through the discovery of a strain of rabbits designated Watanabe heritable hyperlipidemic (WHHL). In these animals massive hypercholesterolemia results from a single genetic defect, and fulminant atherosclerosis occurs despite the ingestion of a cholesterol-free diet. The defect in WHHL rabbits resides in the gene for the low-density-lipoprotein (LDL) receptor-the same gene that is defective in patients with familial hypercholesterolemia. WHHL rabbits, like patients with familial hypercholesterolemia, have a pure elevation in lipoproteins that carry endogenous cholesterol. Moreover, a pattern of atherosclerosis develops that is indistinguishable from the pattern in the human disease. Studies of the WHHL rabbit have highlighted the important part that LDL receptors in the liver play in controlling both the production and the clearance of lipoproteins that carry endogenous cholesterol. These findings have implications for the prevention and treatment of atherosclerosis not only in patients with familial hypercholesterolemia but also in patients with more common forms of hypercholesterolemia.

Original languageEnglish (US)
Pages (from-to)288-296
Number of pages9
JournalNew England Journal of Medicine
Volume309
Issue number5
StatePublished - 1983

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Lipoprotein Receptors
Hyperlipoproteinemia Type II
Atherosclerosis
Hypercholesterolemia
Rabbits
LDL Receptors
Cholesterol
Lipoproteins
Genes
Animal Models
Eating
Diet
Liver

ASJC Scopus subject areas

  • Medicine(all)

Cite this

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abstract = "A new animal model for endogenous hypercholesterolemia has recently become available through the discovery of a strain of rabbits designated Watanabe heritable hyperlipidemic (WHHL). In these animals massive hypercholesterolemia results from a single genetic defect, and fulminant atherosclerosis occurs despite the ingestion of a cholesterol-free diet. The defect in WHHL rabbits resides in the gene for the low-density-lipoprotein (LDL) receptor-the same gene that is defective in patients with familial hypercholesterolemia. WHHL rabbits, like patients with familial hypercholesterolemia, have a pure elevation in lipoproteins that carry endogenous cholesterol. Moreover, a pattern of atherosclerosis develops that is indistinguishable from the pattern in the human disease. Studies of the WHHL rabbit have highlighted the important part that LDL receptors in the liver play in controlling both the production and the clearance of lipoproteins that carry endogenous cholesterol. These findings have implications for the prevention and treatment of atherosclerosis not only in patients with familial hypercholesterolemia but also in patients with more common forms of hypercholesterolemia.",
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