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ApoA-I deficiency causes both hypertriglyceridemia and increased atherosclerosis in human apoB transgenic mice. 1998

E Voyiaziakis, and I J Goldberg, and A S Plump, and E M Rubin, and J L Breslow, and L S Huang
Department of Medicine, Columbia University, College of Physicians & Surgeons, New York, NY 10032, USA.

To study the role of low levels of high density lipoprotein (HDL) and apolipoprotein (apo) A-I in atherosclerosis risk, human apoB transgenic mice (HuBTg) were crossed with apoA-I-deficient (apoA-I-/-) mice. After a high fat challenge, total cholesterol levels increased drastically due to an increase in the non-HDL cholesterol as confirmed by FPLC analysis. In addition, total cholesterol levels in A-I-/- HuBTg mice were lower than the control HuBTg mice, due mainly to decreased HDL-C in A-I-/- HuBTg mice. Analysis of atherosclerosis in the proximal aorta in mice fed a high-fat Western-type diet for 27 weeks revealed a 200% greater lesion area in female apoA-I-/- HuBTg mice (49740+/-9751 microm2) compared to control HuBTg mice (23320+/-4981 microm2, P = 0.03). Lesion size (12380+/-3281 microm2) in male A-I-/- HuBTg mice was also about 200% greater than that in the control HuBTg mice (5849+/-1543 microm2), although not statistically significant. Very few and small lesions were observed in both apoA-I-/- HuBTg and control HuBTg animals fed a chow diet. Therefore, the adverse effect of low HDL on atherosclerosis in mice was only evident when LDL-cholesterol was markedly elevated by high-fat challenge. Male apoA-I-/- HuBTg mice exhibited hypertriglyceridemia when challenged with a high-fat diet. This correlated with both a reduction in lipoprotein lipase activity and a decrease in lipoprotein lipase activation by HDL. In summary, low high density lipoprotein levels due to apolipoprotein A-I deficiency exacerbated the development of atherosclerotic lesions in mice with elevated atherogenic lipoproteins. This mouse model mimics human conditions associated with low HDL levels and provides additional evidence for the anti-atherogenic role of apoA-I.

UI MeSH Term Description Entries
D008071 Lipoprotein Lipase An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. The enzyme hydrolyzes triacylglycerols in chylomicrons, very-low-density lipoproteins, low-density lipoproteins, and diacylglycerols. It occurs on capillary endothelial surfaces, especially in mammary, muscle, and adipose tissue. Genetic deficiency of the enzyme causes familial hyperlipoproteinemia Type I. (Dorland, 27th ed) EC 3.1.1.34. Heparin-Clearing Factor,Lipemia-Clearing Factor,Diacylglycerol Lipase,Diglyceride Lipase,Post-Heparin Lipase,Postheparin Lipase,Postheparin Lipoprotein Lipase,Factor, Heparin-Clearing,Factor, Lipemia-Clearing,Heparin Clearing Factor,Lipase, Diacylglycerol,Lipase, Diglyceride,Lipase, Lipoprotein,Lipase, Post-Heparin,Lipase, Postheparin,Lipase, Postheparin Lipoprotein,Lipemia Clearing Factor,Lipoprotein Lipase, Postheparin,Post Heparin Lipase
D008076 Cholesterol, HDL Cholesterol which is contained in or bound to high-density lipoproteins (HDL), including CHOLESTEROL ESTERS and free cholesterol. High Density Lipoprotein Cholesterol,Cholesterol, HDL2,Cholesterol, HDL3,HDL Cholesterol,HDL(2) Cholesterol,HDL(3) Cholesterol,HDL2 Cholesterol,HDL3 Cholesterol,alpha-Lipoprotein Cholesterol,Cholesterol, alpha-Lipoprotein,alpha Lipoprotein Cholesterol
D008078 Cholesterol, LDL Cholesterol which is contained in or bound to low density lipoproteins (LDL), including CHOLESTEROL ESTERS and free cholesterol. LDL Cholesterol,Cholesteryl Linoleate, LDL,LDL Cholesteryl Linoleate,Low Density Lipoprotein Cholesterol,beta-Lipoprotein Cholesterol,Cholesterol, beta-Lipoprotein,beta Lipoprotein Cholesterol
D008297 Male Males
D008822 Mice, Transgenic Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN. Transgenic Mice,Founder Mice, Transgenic,Mouse, Founder, Transgenic,Mouse, Transgenic,Mice, Transgenic Founder,Transgenic Founder Mice,Transgenic Mouse
D002784 Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Epicholesterol
D004041 Dietary Fats Fats present in food, especially in animal products such as meat, meat products, butter, ghee. They are present in lower amounts in nuts, seeds, and avocados. Fats, Dietary,Dietary Fat,Fat, Dietary
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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