Journal article
Overexpression of human ABCG1 does not affect atherosclerosis in fat-fed ApoE-deficient mice
Arteriosclerosis, Thrombosis, and Vascular Biology, Vol.28(10), pp.1731-1737
2008
Abstract
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. © 2008 American Heart Association, Inc.
Details
- Title
- Overexpression of human ABCG1 does not affect atherosclerosis in fat-fed ApoE-deficient mice
- Authors
- B Burgess (Author) - University of British Columbia, CanadaK Naus (Author) - University of British Columbia, CanadaJ Chan (Author) - University of British Columbia, CanadaV Hirsch-Reinshagen (Author) - University of British Columbia, CanadaG Tansley (Author) - University of British Columbia, CanadaL Matzke (Author) - University of British Columbia, CanadaB Chan (Author) - University of British Columbia, CanadaA Wilkinson (Author) - University of British Columbia, CanadaJ Fan (Author) - University of British Columbia, CanadaJames J Donkin (Author) - University of British Columbia, CanadaD Balik (Author) - University of British Columbia, CanadaT Tanaka (Author) - University of British Columbia, CanadaG Ou (Author) - University of British Columbia, CanadaR Dyer (Author) - University of British Columbia, CanadaS Innis (Author) - University of British Columbia, CanadaB McManus (Author) - University of British Columbia, CanadaD Lütjohann (Author) - University of British Columbia, CanadaC Wellington (Author) - University of British Columbia, Canada
- Publication details
- Arteriosclerosis, Thrombosis, and Vascular Biology, Vol.28(10), pp.1731-1737
- Publisher
- Lippincott Williams & Wilkins
- Date published
- 2008
- DOI
- 10.1161/ATVBAHA.108.168542
- ISSN
- 1079-5642
- Organisation Unit
- UniSC Clinical Trials Centre; University of the Sunshine Coast, Queensland
- Language
- English
- Record Identifier
- 99451301902621
- Output Type
- Journal article
Metrics
610 Record Views
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- Domestic collaboration
- International collaboration
- Web Of Science research areas
- Hematology
- Peripheral Vascular Disease
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Source: InCites