This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 28/10/1731    most recent ATVBAHA.108.168542v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Burgess, B. Articles by Wellington, C. Search for Related Content PubMed PubMed Citation Articles by Burgess, B. Articles by Wellington, C.

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:1731.)
© 2008 American Heart Association, Inc.

Integrative Physiology/Experimental Medicine

Overexpression of Human ABCG1 Does Not Affect Atherosclerosis in Fat-Fed ApoE-Deficient Mice

Braydon Burgess; Kathryn Naus; Jeniffer Chan; Veronica Hirsch-Reinshagen; Gavin Tansley; Lisa Matzke; Benny Chan; Anna Wilkinson; Jianjia Fan; James Donkin; Danielle Balik; Tracie Tanaka; George Ou; Roger Dyer; Sheila Innis; Bruce McManus; Dieter Lütjohann; Cheryl Wellington

From the Department of Pathology and Laboratory Medicine (B.B., K.N., J.C., V.H.-R., G.T., A.W., J.F., J.D., D.B., T.T., G.O., C.W.), Child and Family Research Institute, University of British Columbia, Vancouver, Canada; ICapture Centre (L.M., B.M.), University of British Columbia, Vancouver, Canada; the Department of Pediatrics (B.C., R.D., S.I.), Child and Family Research Institute, University of British Columbia, Vancouver, Canada; and the Department of Clinical Pharmacology (D.L.), University of Bonn, Germany.

Correspondence to Dr Cheryl L. Wellington, Department of Pathology and Laboratory Medicine, University of British Columbia, 980 West 28th Avenue, Vancouver, British Columbia, Canada. E-mail Cheryl{at}cmmt.ubc.ca

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.

We developed transgenic mice expressing functional human ABCG1. Elevated ABCG1 levels did not affect plasma lipids, macrophage cholesterol efflux, atherosclerotic lesion area in apoE^–/– mice, or levels of tissue cholesterol, cholesterol ester, phospholipids, or triglycerides. Transgenic ABCG1 was, however, associated with altered sterol intermediate levels in liver.

Key Words: ABCG1 • cholesterol • atherosclerosis • cholesterol intermediate