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Pathophysiology of apolipoprotein E deficiency in mice: relevance to apo E‐related disorders in humans
Author(s) -
Moghadasian Mohammed H.,
McManus Bruce M.,
Nguyen Lien B.,
Shefer Sarah,
Nadji Mehrdad,
Godin David V.,
Green Thomas J.,
Hill John,
Yang Yingying,
Scudamore Charles H.,
Frohlich Jiri J.
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.01-0463com
Subject(s) - endocrinology , medicine , apolipoprotein e , hepatic lipase , apolipoprotein b , dyslipidemia , lipoprotein lipase , lipoprotein , cholesterol , triglyceride , pathophysiology , biology , disease , adipose tissue
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 atherogene‐sis without affecting lipase activities, endogenous anti‐oxidant 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., Scud‐amore C. H., Frohlich J. J. Pathophysiology of apoli‐poprotein E deficiency in mice: relevance to apo E‐related disorders in humans. FASEB J. 15, 2623–2630 (2001)