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Departments of
* Pathology and Laboratory Medicine (Healthy Heart Program and the iCAPTUR4E Centre),
Pharmacology and
Surgery, University of British Columbia, Vancouver, B.C, Canada;
Department of Medicine, UMDNJ, Rutgers, New Jersey 08901, USA; and
Department of Pathology, University of Miami, Miami, Florida 33101, USA
1Correspondence: Healthy Heart Program, 180 St. Paul’s Hospital, 1081 Burrard St., Vancouver, BC, Canada V6Z 1Y6. E-mail: mhmoghad{at}interchange.ubc.ca
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.—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. Pathophysiology of apolipoprotein E deficiency in mice: relevance to apo E-related disorders in humans.
Key Words: apo E • brain • antioxidants • atherosclerosis • xanthomatosis • lipids
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