Overexpression of human ABCG1 does not affect atherosclerosis in fat-fed ApoE-deficient mice

被引：58

作者：

Burgess, Braydon ^{[1
]}

Naus, Kathryn ^{[1
]}

Chan, Jeniffer ^{[1
]}

Hirsch-Reinshagen, Veronica ^{[1
]}

Tansley, Gavin ^{[1
]}

Matzke, Lisa ^{[2
]}

Chan, Benny ^{[3
]}

Wilkinson, Anna ^{[1
]}

Fan, Jianjia ^{[1
]}

Donkin, James ^{[1
]}

Balik, Danielle ^{[1
]}

Tanaka, Tracie ^{[1
]}

Ou, George ^{[1
]}

Dyer, Roger ^{[3
]}

Innis, Sheila ^{[3
]}

McManus, Bruce ^{[2
]}

Luetjohann, Dieter ^{[4
]}

Wellington, Cheryl ^{[1
]}

机构：

[1] Univ British Columbia, Dept Pathol & Lab Med, Child & Family Res Inst, Vancouver, BC V5Z 1M9, Canada

[2] Univ British Columbia, ICapture Ctr, Vancouver, BC V5Z 1M9, Canada

[3] Univ British Columbia, Dept Pediat, Child & Family Res Inst, Vancouver, BC V5Z 1M9, Canada

[4] Univ Bonn, Dept Clin Pharmacol, D-5300 Bonn, Germany

来源：

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY | 2008年 / 28卷 / 10期

基金：

加拿大健康研究院;

关键词：

ABCG1; cholesterol; atherosclerosis; cholesterol intermediate;

D O I：

10.1161/ATVBAHA.108.168542

中图分类号：

R5 [内科学];

学科分类号：

1002 [临床医学]; 100201 [内科学];

摘要：

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.

引用

页码：1731 / 1737

页数：7

共 39 条

[1]

Increased atherosclerosis in hyperlipidemic mice with inactivation of ABCA1 in macrophages [J].

Aiello, RJ ;

Brees, D ;

Bourassa, PA ;

Royer, L ;

Lindsey, S ;

Coskran, T ;

Haghpassand, M ;

Francone, OL .

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2002, 22 (04) :630-637

[2]

Impaired development of atherosclerosis in hyperlipidemic Ldlr-/- and ApoE -/- mice transplanted with Abcg1-/- bone marrow [J].

Baldan, Angela ;

Pei, Liming ;

Lee, Richard ;

Tarr, Paul ;

Tangirala, Rajendra K. ;

Weinstein, Michael M. ;

Frank, Joy ;

Li, Andrew C. ;

Tontonoz, Peter ;

Edwards, Peter A. .

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2006, 26 (10) :2301-2307

[3]

Enhanced ABCG1 expression increases atherosclerosis in LDLr-KO mice on a western diet [J].

Basso, Federica ;

Amar, Marcelo J. ;

Wagner, Elke M. ;

Vaisman, Boris ;

Paigen, Beverly ;

Santamarina-Fojo, Silvia ;

Remaley, Alan T. .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2006, 351 (02) :398-404

[4]

The gene encoding ATP-binding cassette transporter 1 is mutated in Tangier disease [J].

Bodzioch, M ;

Orsó, E ;

Klucken, T ;

Langmann, T ;

Böttcher, L ;

Diederich, W ;

Drobnik, W ;

Barlage, S ;

Büchler, C ;

Porsch-Özcürümez, M ;

Kaminski, WE ;

Hahmann, HW ;

Oette, K ;

Rothe, G ;

Aslanidis, C ;

Lackner, KJ ;

Schmitz, G .

NATURE GENETICS, 1999, 22 (04) :347-351

[5]

BREWER HB, 2003, AM J CARDIOL, V91, P3

[6]

Mutations in ABC1 in Tangier disease and familial high-density lipoprotein deficiency [J].

Brooks-Wilson, A ;

Marcil, M ;

Clee, SM ;

Zhang, LH ;

Roomp, K ;

van Dam, M ;

Yu, L ;

Brewer, C ;

Collins, JA ;

Molhuizen, HOF ;

Loubser, O ;

Ouelette, BFF ;

Fichter, K ;

Ashbourne-Excoffon, KJD ;

Sensen, CW ;

Scherer, S ;

Mott, S ;

Denis, M ;

Martindale, D ;

Frohlich, J ;

Morgan, K ;

Koop, B ;

Pimstone, S ;

Kastelein, JJP ;

Genest, J ;

Hayden, MR .

NATURE GENETICS, 1999, 22 (04) :336-345

[7]

Intestinal ABCA1 directly contributes to HDL biogenesis in vivo [J].

Brunham, LR ;

Kruit, JK ;

Iqbal, J ;

Fievet, C ;

Timmins, JM ;

Pape, TD ;

Coburn, BA ;

Bissada, N ;

Staels, B ;

Groen, AK ;

Hussain, MM ;

Parks, JS ;

Kuipers, F ;

Hayden, MR .

JOURNAL OF CLINICAL INVESTIGATION, 2006, 116 (04) :1052-1062

[8]

Isolation and characterization of a mammalian homolog of the Drosophila white gene [J].

Croop, JM ;

Tiller, GE ;

Fletcher, JA ;

Lux, ML ;

Raab, E ;

Goldenson, D ;

Son, D ;

Arciniegas, S ;

Wu, RL .

GENE, 1997, 185 (01) :77-85

[9]

Dean M, 2001, J LIPID RES, V42, P1007

[10]

Genetics of ATP-binding cassette transporters [J].

Dean, M .

PHASE II CONJUGATION ENZYMES AND TRANSPORT SYSTEMS, 2005, 400 :409-429

← 1 2 3 4 →