OBJECTIVE: The purpose of this study was to evaluate the effects of whole body overexpression of human ABCG1 on atherosclerosis in apoE(-/-) mice. METHODS AND RESULTS: We generated BAC transgenic mice in which human ABCG1 is expressed from endogenous regulatory signals, leading to a 3- to 7-fold increase in ABCG1 protein across various tissues. Although the ABCG1 BAC transgene rescued lung lipid accumulation in ABCG1(-/-) mice, it did not affect plasma lipid levels, macrophage cholesterol efflux to HDL, atherosclerotic lesion area in apoE(-/-) mice, or levels of tissue cholesterol, cholesterol ester, phospholipids, or triglycerides. Subtle changes in sterol biosynthetic intermediate levels were observed in liver, with chow-fed ABCG1 BAC Tg mice showing a nonsignificant trend toward decreased levels of lathosterol, lanosterol, and desmosterol, and fat-fed mice exhibiting significantly elevated levels of each intermediate. These changes were insufficient to alter ABCA1 expression in liver. CONCLUSIONS: Transgenic human ABCG1 does not influence atherosclerosis in apoE(-/-) mice but may participate in the regulation of tissue cholesterol biosynthesis.
OBJECTIVE: The purpose of this study was to evaluate the effects of whole body overexpression of humanABCG1 on atherosclerosis in apoE(-/-) mice. METHODS AND RESULTS: We generated BAC transgenic mice in which humanABCG1 is expressed from endogenous regulatory signals, leading to a 3- to 7-fold increase in ABCG1 protein across various tissues. Although the ABCG1 BAC transgene rescued lung lipid accumulation in ABCG1(-/-) mice, it did not affect plasma lipid levels, macrophage cholesterol efflux to HDL, atherosclerotic lesion area in apoE(-/-) mice, or levels of tissue cholesterol, cholesterol ester, phospholipids, or triglycerides. Subtle changes in sterol biosynthetic intermediate levels were observed in liver, with chow-fed ABCG1 BAC Tg mice showing a nonsignificant trend toward decreased levels of lathosterol, lanosterol, and desmosterol, and fat-fed mice exhibiting significantly elevated levels of each intermediate. These changes were insufficient to alter ABCA1 expression in liver. CONCLUSIONS: Transgenic humanABCG1 does not influence atherosclerosis in apoE(-/-) mice but may participate in the regulation of tissue cholesterol biosynthesis.
Authors: Robert S Rosenson; H Bryan Brewer; Philip J Barter; Johan L M Björkegren; M John Chapman; Daniel Gaudet; Daniel Seung Kim; Eric Niesor; Kerry-Anne Rye; Frank M Sacks; Jean-Claude Tardif; Robert A Hegele Journal: Nat Rev Cardiol Date: 2017-08-10 Impact factor: 32.419
Authors: Cheng-I J Ma; Jennifer A Beckstead; Airlia Thompson; Anouar Hafiane; Rui Hao Leo Wang; Robert O Ryan; Robert S Kiss Journal: Biochem Cell Biol Date: 2012-05-18 Impact factor: 3.626
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