Pathophysiology of apolipoprotein E deficiency in mice: relevance to apo E-related disorders in humans
Pathophysiology of apolipoprotein E deficiency in mice: relevance to apo E-related disorders in humans
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DOI：
10.1096/fj.01-0463com
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发表时间：
2001-12-01
期刊：
影响因子：
4.8
通讯作者：
Frohlich, JJ
中科院分区：
文献类型：
--
作者：
Moghadasian, MH;McManus, BM;Frohlich, JJ
载脂蛋白E（apo E）缺乏（或其在人类中的异常）与一系列病理状况相关，包括血脂异常、动脉粥样硬化、阿尔茨海默病和寿命缩短。本研究的目的是描述载脂蛋白E缺陷C57 BL/6 J小鼠的这些条件，并将其与人类疾病联系起来。载脂蛋白E基因的缺失与小鼠脂蛋白代谢[血浆总胆固醇（TC）（>+400%）、HDL胆固醇（-80%）、HDL/TC和HDL/LDL比值]的变化有关（分别为-93%和-96%），apo B耗尽血浆中的酯化率（+100%），血浆甘油三酯（+200%），肝HMG-CoA还原酶活性（-50%），肝胆固醇含量（+30%）]、血浆同型半胱氨酸和葡萄糖水平降低以及严重的动脉粥样硬化和皮肤黄瘤病。肝脏和脂蛋白脂肪酶活性、肝脏LDL受体功能和器官抗氧化能力保持不变。几种组织学/免疫组织学染色未能检测到37周龄雄性apo E-KO小鼠脑中神经退行性疾病的潜在标志物。载脂蛋白E-KO小鼠可能有正常的生长和发育，但晚期动脉粥样硬化和黄瘤病可能间接减少其寿命。载脂蛋白E在37周龄雄性小鼠的脂质代谢和动脉粥样硬化形成的调节中起着至关重要的作用，而不影响脂肪酶活性、内源性抗氧化能力或神经退行性标志物的出现。
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.