Pathophysiology of apolipoprotein E deficiency in mice: Relevance to apo E-related disorders in humans

M. H. Moghadasian, B. M. McManus, L. B. Nguyen, S. Shefer, M. Nadji, D. V. Godin, T. J. Green, J. Hill, Y. Yang, C. H. Scudamore, J. J. Frohlich

Research output: Contribution to journalArticle

110 Scopus citations

Abstract

Apolipoprotein E (apo E) deficiency (or its abnormalities in humans) is associated with a series of pathological conditions including dyslipidemia, atherosclerosis, Alzheimer's disease, and shorter life span. The purpose of this study was to characterize these conditions in apo E-deficient C57BL/6J mice and relate them to human disorders. Deletion of apo E gene in mice is associated with changes in lipoprotein metabolism [plasma total cholesterol (TC) (>+400%), HDL cholesterol (-80%), HDL/TC, and HDL/LDL ratios (-93% and -96%, respectively), esterification rate in apo B-depleted plasma (+100%), plasma triglyceride (+200%), hepatic HMG-CoA reductase activity (-50%), hepatic cholesterol content (+30%)], decreased plasma homocyst(e)ine and glucose levels, and severe atherosclerosis and cutaneous xanthomatosis. Hepatic and lipoprotein lipase activities, hepatic LDL receptor function, and organ antioxidant capacity remain unchanged. Several histological/immunohistological stainings failed to detect potential markers for neurodegenerative disease in the brain of 37-wk-old male apo E-KO mice. Apo E-KO mice may have normal growth and development, but advanced atherosclerosis and xanthomatosis may indirectly reduce their life span. Apo E plays a crucial role in regulation of lipid metabolism and atherogenesis without affecting lipase activities, endogenous antioxidant capacity, or appearance of neurodegenerative markers in 37-wk-old male mice.

Original languageEnglish (US)
Pages (from-to)2623-2630
Number of pages8
JournalFASEB Journal
Volume15
Issue number14
DOIs
StatePublished - Dec 22 2001
Externally publishedYes

Keywords

  • Antioxidants
  • Apo E
  • Atherosclerosis
  • Brain
  • Lipids
  • Xanthomatosis

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

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    Moghadasian, M. H., McManus, B. M., Nguyen, L. B., Shefer, S., Nadji, M., Godin, D. V., Green, T. J., Hill, J., Yang, Y., Scudamore, C. H., & Frohlich, J. J. (2001). Pathophysiology of apolipoprotein E deficiency in mice: Relevance to apo E-related disorders in humans. FASEB Journal, 15(14), 2623-2630. https://doi.org/10.1096/fj.01-0463com