title: Pathophysiology of apolipoprotein E deficiency in mice: relevance to apo E-related disorders in humans.
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.
authors.affiliation: Department of Pathology, (Healthy Heart Program and the iCAPTUR4E Centre), University of British Columbia, Vancouver, B.C, Canada. mhmoghad@interchange.ubc.ca
authors.forename: M H
authors.initials: MH
authors.lastname: Moghadasian
authors.forename: B M
authors.initials: BM
authors.lastname: McManus
authors.forename: L B
authors.initials: LB
authors.lastname: Nguyen
authors.forename: S
authors.initials: S
authors.lastname: Shefer
authors.forename: M
authors.initials: M
authors.lastname: Nadji
authors.forename: D V
authors.initials: DV
authors.lastname: Godin
authors.forename: T J
authors.initials: TJ
authors.lastname: Green
authors.forename: J
authors.initials: J
authors.lastname: Hill
authors.forename: Y
authors.initials: Y
authors.lastname: Yang
authors.forename: C H
authors.initials: CH
authors.lastname: Scudamore
authors.forename: J J
authors.initials: JJ
authors.lastname: Frohlich
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000502:physiology; D001921:Brain / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D004951:Esterification; D005838:Genotype; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D006710:Homocysteine / Q000097:blood; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D006949:Hyperlipidemias / Q000097:blood / Q000503:physiopathology; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism; D008049:Lipase / Q000097:blood; D008055:Lipids / Q000097:blood; D008075:Lipoproteins, HDL / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016900:Neurofilament Proteins / Q000032:analysis; D011973:Receptors, LDL / Q000502:physiology; D016019:Survival Analysis; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D000975:Antioxidants; D001057:Apolipoproteins E; D001786:Blood Glucose; D005904:Glial Fibrillary Acidic Protein; D008055:Lipids; D008075:Lipoproteins, HDL; D016900:Neurofilament Proteins; D011973:Receptors, LDL; D006710:Homocysteine; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D008049:Lipase