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: 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
• Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J) Vol. 15 Issue 14 Pg. 2623-30 (Dec 2001) ISSN: 1530-6860 [Electronic] United States
• PMID: 11726538 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Antioxidants
• Apolipoproteins E
• Blood Glucose
• Glial Fibrillary Acidic Protein
• Lipids
• Lipoproteins, HDL
• Neurofilament Proteins
• Receptors, LDL
• Homocysteine
• Cholesterol
• Hydroxymethylglutaryl CoA Reductases
• Lipase

Topics

• Animals
• Antioxidants (metabolism)
• Apolipoproteins E (deficiency, genetics)
• Blood Glucose (metabolism)
• Body Weight (physiology)
• Brain (metabolism)
• Cholesterol (metabolism)
• Esterification
• Genotype
• Glial Fibrillary Acidic Protein (analysis)
• Homocysteine (blood)
• Humans
• Hydroxymethylglutaryl CoA Reductases (metabolism)
• Hyperlipidemias (blood, physiopathology)
• Immunohistochemistry
• Kidney (metabolism)
• Lipase (blood)
• Lipids (blood)
• Lipoproteins, HDL (metabolism)
• Liver (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Neurofilament Proteins (analysis)
• Receptors, LDL (physiology)
• Survival Analysis
• Time Factors
• Tissue Distribution