This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 26/10/2308    most recent 01.ATV.0000242275.92915.43v1 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 HighWire Citing Articles via Google Scholar Google Scholar Articles by Ranalletta, M. Articles by Tall, A. R. Search for Related Content PubMed PubMed Citation Articles by Ranalletta, M. Articles by Tall, A. R. Related Collections Related Article

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:2308.)
© 2006 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Decreased Atherosclerosis in Low-Density Lipoprotein Receptor Knockout Mice Transplanted With Abcg1^–/– Bone Marrow

Mollie Ranalletta; Nan Wang; Seongah Han; Laurent Yvan-Charvet; Carrie Welch; Alan R. Tall

From the Department of Medicine, Columbia University, New York.

Correspondence to Mollie Ranalletta, Division of Molecular Medicine, Department of Medicine, Columbia University, 630 West 168th St, New York, NY 10032. E-mail mr2375{at}columbia.edu

Objective— Recent studies indicate that the ATP-binding cassette transporter ABCG1 can promote cholesterol efflux from macrophages to high-density lipoprotein. This study was designed to assess the in vivo role of macrophage ABCG1 in atherosclerosis.

Methods and Results— Bone marrow from Abcg1^–/– mice was transplanted into irradiated Ldlr^–/– recipients, and atherosclerosis was evaluated by aortic root assay after 7 or 11 weeks of feeding on a Western diet. After 7 weeks, there was no difference in lesion area in mice receiving either wild-type or Abcg1^–/– bone marrow, whereas after 11 weeks, lesion area was moderately but significantly reduced in Abcg1^–/– recipients. ABCG1-deficient peritoneal macrophages showed induction of several liver X receptor target genes, such as Abca1 and Srebp1c, and a dramatic increase in apolipoprotein E (apoE) protein both in cell media and lysates, without parallel change in apoE mRNA. Abca1 knockdown prevented the increase in apoE secretion but had minimal effects on apoE accumulation in cell lysates of Abcg1^–/– macrophages. Plasma apoE levels were markedly increased in recipients of Abcg1^–/– bone marrow.

Conclusions— These studies reveal an inverse relationship between Abcg1 expression and apoE accumulation and secretion in macrophages. The reduced atherosclerosis in recipients of Abcg1-deficient bone marrow may be explained by induction of Abca1 and an associated increase in macrophage apoE secretion.

We examined the role of ABCG1 in atherosclerosis. Ldlr^–/– mice transplanted with Abcg1^–/– bone marrow showed decreased atherosclerosis after 11 weeks of Western diet, reflecting compensatory induction of Abca1 and apoE secretion by Abcg1^–/– macrophages. These studies reveal an inverse relationship between Abcg1 expression and apoE accumulation and secretion in macrophages.

Key Words: atherosclerosis • ABC transporters • apoE • macrophages

Related Article:

Is Two out of Three Enough for ABCG1?

Linda K. Curtiss
Arterioscler Thromb Vasc Biol 2006 26: 2175-2177. [Extract] [Full Text] [PDF]

This article has been cited by other articles:

				J. Liu, C. Huan, M. Chakraborty, H. Zhang, D. Lu, M.-S. Kuo, G. Cao, and X.-C. Jiang Macrophage Sphingomyelin Synthase 2 Deficiency Decreases Atherosclerosis in Mice Circ. Res., July 31, 2009; 105(3): 295 - 303. [Abstract] [Full Text] [PDF]

				A. Baldan, D. D. Bojanic, and P. A. Edwards The ABCs of sterol transport J. Lipid Res., April 1, 2009; 50(Supplement): S80 - S85. [Abstract] [Full Text] [PDF]

				D. J. Rader, E. T. Alexander, G. L. Weibel, J. Billheimer, and G. H. Rothblat The role of reverse cholesterol transport in animals and humans and relationship to atherosclerosis J. Lipid Res., April 1, 2009; 50(Supplement): S189 - S194. [Abstract] [Full Text] [PDF]

				M. L. Lindegaard, C. A. Wassif, B. Vaisman, M. Amar, E. V. Wasmuth, R. Shamburek, L. B. Nielsen, A. T. Remaley, and F. D. Porter Characterization of placental cholesterol transport: ABCA1 is a potential target for in utero therapy of Smith-Lemli-Opitz syndrome Hum. Mol. Genet., December 1, 2008; 17(23): 3806 - 3813. [Abstract] [Full Text] [PDF]

				L. Yvan-Charvet, C. Welch, T. A. Pagler, M. Ranalletta, M. Lamkanfi, S. Han, M. Ishibashi, R. Li, N. Wang, and A. R. Tall Increased Inflammatory Gene Expression in ABC Transporter-Deficient Macrophages: Free Cholesterol Accumulation, Increased Signaling via Toll-Like Receptors, and Neutrophil Infiltration of Atherosclerotic Lesions Circulation, October 28, 2008; 118(18): 1837 - 1847. [Abstract] [Full Text] [PDF]

				B. Burgess, K. Naus, J. Chan, V. Hirsch-Reinshagen, G. Tansley, L. Matzke, B. Chan, A. Wilkinson, J. Fan, J. Donkin, et al. Overexpression of Human ABCG1 Does Not Affect Atherosclerosis in Fat-Fed ApoE-Deficient Mice Arterioscler Thromb Vasc Biol, October 1, 2008; 28(10): 1731 - 1737. [Abstract] [Full Text] [PDF]

				B. L. Burgess, P. F. Parkinson, M. M. Racke, V. Hirsch-Reinshagen, J. Fan, C. Wong, S. Stukas, L. Theroux, J. Y. Chan, J. Donkin, et al. ABCG1 influences the brain cholesterol biosynthetic pathway but does not affect amyloid precursor protein or apolipoprotein E metabolism in vivo J. Lipid Res., June 1, 2008; 49(6): 1254 - 1267. [Abstract] [Full Text] [PDF]

				M. Kockx, W. Jessup, and L. Kritharides Regulation of Endogenous Apolipoprotein E Secretion by Macrophages Arterioscler Thromb Vasc Biol, June 1, 2008; 28(6): 1060 - 1067. [Abstract] [Full Text] [PDF]

				J. P. Mauldin, M. H. Nagelin, A. J. Wojcik, S. Srinivasan, M. D. Skaflen, C. R. Ayers, C. A. McNamara, and C. C. Hedrick Reduced Expression of ATP-Binding Cassette Transporter G1 Increases Cholesterol Accumulation in Macrophages of Patients With Type 2 Diabetes Mellitus Circulation, May 27, 2008; 117(21): 2785 - 2792. [Abstract] [Full Text] [PDF]

				N. Wang, L. Yvan-Charvet, D. Lutjohann, M. Mulder, T. Vanmierlo, T.-W. Kim, and A. R. Tall ATP-binding cassette transporters G1 and G4 mediate cholesterol and desmosterol efflux to HDL and regulate sterol accumulation in the brain FASEB J, April 1, 2008; 22(4): 1073 - 1082. [Abstract] [Full Text] [PDF]

				A. J. Wojcik, M. D. Skaflen, S. Srinivasan, and C. C. Hedrick A Critical Role for ABCG1 in Macrophage Inflammation and Lung Homeostasis J. Immunol., March 15, 2008; 180(6): 4273 - 4282. [Abstract] [Full Text] [PDF]

				R. Out, M. Hoekstra, K. Habets, I. Meurs, V. de Waard, R. B. Hildebrand, Y. Wang, G. Chimini, J. Kuiper, T. J.C. Van Berkel, et al. Combined Deletion of Macrophage ABCA1 and ABCG1 Leads to Massive Lipid Accumulation in Tissue Macrophages and Distinct Atherosclerosis at Relatively Low Plasma Cholesterol Levels Arterioscler Thromb Vasc Biol, February 1, 2008; 28(2): 258 - 264. [Abstract] [Full Text] [PDF]

				D. Yan, M. I. Mayranpaa, J. Wong, J. Perttila, M. Lehto, M. Jauhiainen, P. T. Kovanen, C. Ehnholm, A. J. Brown, and V. M. Olkkonen OSBP-related Protein 8 (ORP8) Suppresses ABCA1 Expression and Cholesterol Efflux from Macrophages J. Biol. Chem., January 4, 2008; 283(1): 332 - 340. [Abstract] [Full Text] [PDF]

				L. Yvan-Charvet, T. A. Pagler, N. Wang, T. Senokuchi, M. Brundert, H. Li, F. Rinninger, and A. R. Tall SR-BI inhibits ABCG1-stimulated net cholesterol efflux from cells to plasma HDL J. Lipid Res., January 1, 2008; 49(1): 107 - 114. [Abstract] [Full Text] [PDF]

				A. J. Lusis, J. Yu, and S. S. Wang The Problem of Passenger Genes in Transgenic Mice Arterioscler Thromb Vasc Biol, October 1, 2007; 27(10): 2100 - 2103. [Abstract] [Full Text] [PDF]

				N. Terasaka, N. Wang, L. Yvan-Charvet, and A. R. Tall High-density lipoprotein protects macrophages from oxidized low-density lipoprotein-induced apoptosis by promoting efflux of 7-ketocholesterol via ABCG1 PNAS, September 18, 2007; 104(38): 15093 - 15098. [Abstract] [Full Text] [PDF]

				M. Kockx, D. L. Guo, T. Huby, P. Lesnik, J. Kay, T. Sabaretnam, E. Jary, M. Hill, K. Gaus, J. Chapman, et al. Secretion of Apolipoprotein E From Macrophages Occurs via a Protein Kinase A and Calcium-Dependent Pathway Along the Microtubule Network Circ. Res., September 14, 2007; 101(6): 607 - 616. [Abstract] [Full Text] [PDF]

				D. Yan, M. Jauhiainen, R. B. Hildebrand, K. Willems van Dijk, T. J.C. Van Berkel, C. Ehnholm, M. Van Eck, and V. M. Olkkonen Expression of Human OSBP-Related Protein 1L in Macrophages Enhances Atherosclerotic Lesion Development in LDL Receptor-Deficient Mice Arterioscler Thromb Vasc Biol, July 1, 2007; 27(7): 1618 - 1624. [Abstract] [Full Text] [PDF]

				L. Yvan-Charvet, F. Matsuura, N. Wang, M. J. Bamberger, T. Nguyen, F. Rinninger, X.-C. Jiang, C. L. Shear, and A. R. Tall Inhibition of Cholesteryl Ester Transfer Protein by Torcetrapib Modestly Increases Macrophage Cholesterol Efflux to HDL Arterioscler Thromb Vasc Biol, May 1, 2007; 27(5): 1132 - 1138. [Abstract] [Full Text] [PDF]

				R. Out, M. Hoekstra, I. Meurs, P. de Vos, J. Kuiper, M. Van Eck, and T. J.C. Van Berkel Total Body ABCG1 Expression Protects Against Early Atherosclerotic Lesion Development in Mice Arterioscler Thromb Vasc Biol, March 1, 2007; 27(3): 594 - 599. [Abstract] [Full Text] [PDF]

				J. F. Oram and A. M. Vaughan ATP-Binding Cassette Cholesterol Transporters and Cardiovascular Disease Circ. Res., November 10, 2006; 99(10): 1031 - 1043. [Abstract] [Full Text] [PDF]

				L. K. Curtiss Is Two out of Three Enough for ABCG1? Arterioscler Thromb Vasc Biol, October 1, 2006; 26(10): 2175 - 2177. [Full Text] [PDF]