This Article Full Text Full Text (PDF) Data Supplement Correction (v23,p1950) All Versions of this Article: 23/9/1589    most recent 01.ATV.0000083343.19940.A0v1 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 Covey, S. D. Articles by Trigatti, B. L. Search for Related Content PubMed PubMed Citation Articles by Covey, S. D. Articles by Trigatti, B. L. Related Collections Pathophysiology Genetically altered mice Lipid and lipoprotein metabolism Other Vascular biology

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:1589.)
© 2003 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Scavenger Receptor Class B Type I–Mediated Protection Against Atherosclerosis in LDL Receptor–Negative Mice Involves Its Expression in Bone Marrow–Derived Cells

Scott D. Covey; Monty Krieger; Wei Wang; Marsha Penman; Bernardo L. Trigatti

From the Department of Biology (M.K., M.P., B.L.T.), Massachusetts Institute of Technology, Cambridge, Mass, and the Department of Biochemistry (S.D.C., W.W., B.L.T.), McMaster University, Hamilton, Ontario, Canada.

Correspondence to Bernardo L. Trigatti, Room HSC-4H35, Department of Biochemistry, McMaster University, Hamilton, Ontario, Canada L8N 3Z5. E-mail trigatt{at}mcmaster.ca

Objective— Scavenger receptor class B type I (SR-BI) is a cell-surface HDL receptor that is implicated in reverse cholesterol transport and protection against atherosclerosis. We have previously demonstrated that SR-BI/apolipoprotein E double-knockout mice develop severe occlusive coronary artery disease and myocardial infarction and die at 6 weeks of age. To determine if this is a general effect of a lack of SR-BI, we generated mice deficient in both SR-BI and the LDL receptor.

Methods and Results— Complete ablation of SR-BI expression in LDL receptor knockout mice resulted in increased plasma cholesterol associated with HDL particles of abnormally large size and a 6-fold increase in diet-induced aortic atherosclerosis but no macroscopic evidence of early-onset coronary artery disease, cardiac pathology, or early death. Furthermore, selective elimination of SR-BI expression in bone marrow–derived cells resulted in increased diet-induced atherosclerosis in LDL receptor knockout mice without concomitant alterations in the distributions of plasma lipoprotein cholesterol.

Conclusions— SR-BI expression protects against atherosclerosis in LDL receptor–deficient as well as apolipoprotein E–deficient mice, and its expression in bone marrow–derived cells contributes to this protection.

Key Words: scavenger receptor class B type I • atherosclerosis • bone marrow transplant • HDL • cholesterol

This article has been cited by other articles:

				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]

				L. Shelly, L. Royer, T. Sand, H. Jensen, and Y. Luo Phospholipid transfer protein deficiency ameliorates diet-induced hypercholesterolemia and inflammation in mice J. Lipid Res., April 1, 2008; 49(4): 773 - 781. [Abstract] [Full Text] [PDF]

				M. Van Eck, M. Hoekstra, R. Out, I. S. T. Bos, J. K. Kruijt, R. B. Hildebrand, and T. J. C. Van Berkel Scavenger receptor BI facilitates the metabolism of VLDL lipoproteins in vivo J. Lipid Res., January 1, 2008; 49(1): 136 - 146. [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]

				X. Zhang, A. N. Moor, K. A. Merkler, Q. Liu, and M. P. McLean Regulation of Alternative Splicing of Liver Scavenger Receptor Class B Gene by Estrogen and the Involved Regulatory Splicing Factors Endocrinology, November 1, 2007; 148(11): 5295 - 5304. [Abstract] [Full Text] [PDF]

				V. R. Babaev, H. Ishiguro, L. Ding, P. G. Yancey, D. E. Dove, W. J. Kovacs, C. F. Semenkovich, S. Fazio, and M. F. Linton Macrophage Expression of Peroxisome Proliferator Activated Receptor-{alpha} Reduces Atherosclerosis in Low-Density Lipoprotein Receptor Deficient Mice Circulation, September 18, 2007; 116(12): 1404 - 1412. [Abstract] [Full Text] [PDF]

				T. J. F. Nieland, J. T. Shaw, F. A. Jaipuri, Z. Maliga, J. L. Duffner, A. N. Koehler, and M. Krieger Influence of HDL-cholesterol-elevating drugs on the in vitro activity of the HDL receptor SR-BI J. Lipid Res., August 1, 2007; 48(8): 1832 - 1845. [Abstract] [Full Text] [PDF]

				S. Agrawal, M. Febbraio, E. Podrez, M. K. Cathcart, G. R. Stark, and G. M. Chisolm Signal Transducer and Activator of Transcription 1 Is Required for Optimal Foam Cell Formation and Atherosclerotic Lesion Development Circulation, June 12, 2007; 115(23): 2939 - 2947. [Abstract] [Full Text] [PDF]

				P. G. Yancey, W. G. Jerome, H. Yu, E. E. Griffin, B. E. Cox, V. R. Babaev, S. Fazio, and M. F. Linton Severely altered cholesterol homeostasis in macrophages lacking apoE and SR-BI J. Lipid Res., May 1, 2007; 48(5): 1140 - 1149. [Abstract] [Full Text] [PDF]

				Y. Zhang, A. M. Ahmed, N. McFarlane, C. Capone, D. R. Boreham, R. Truant, S. A. Igdoura, and B. L. Trigatti Regulation of SR-BI-mediated selective lipid uptake in Chinese hamster ovary-derived cells by protein kinase signaling pathways J. Lipid Res., February 1, 2007; 48(2): 405 - 416. [Abstract] [Full Text] [PDF]

				M. Bukrinsky and D. Sviridov Human immunodeficiency virus infection and macrophage cholesterol metabolism. J. Leukoc. Biol., November 1, 2006; 80(5): 1044 - 1051. [Abstract] [Full Text] [PDF]

				M. Brundert, J. Heeren, M. Bahar-Bayansar, A. Ewert, K. J. Moore, and F. Rinninger Selective uptake of HDL cholesteryl esters and cholesterol efflux from mouse peritoneal macrophages independent of SR-BI J. Lipid Res., November 1, 2006; 47(11): 2408 - 2421. [Abstract] [Full Text] [PDF]

				A. Yesilaltay, O. Kocher, R. Pal, A. Leiva, V. Quinones, A. Rigotti, and M. Krieger PDZK1 Is Required for Maintaining Hepatic Scavenger Receptor, Class B, Type I (SR-BI) Steady State Levels but Not Its Surface Localization or Function J. Biol. Chem., September 29, 2006; 281(39): 28975 - 28980. [Abstract] [Full Text] [PDF]

				K. J. Moore and M. W. Freeman Scavenger Receptors in Atherosclerosis: Beyond Lipid Uptake Arterioscler. Thromb. Vasc. Biol., August 1, 2006; 26(8): 1702 - 1711. [Abstract] [Full Text] [PDF]

				M. Cuchel and D. J. Rader Macrophage Reverse Cholesterol Transport: Key to the Regression of Atherosclerosis? Circulation, May 30, 2006; 113(21): 2548 - 2555. [Full Text] [PDF]

				X.-A. Li, L. Guo, R. Asmis, M. Nikolova-Karakashian, and E. J. Smart Scavenger Receptor BI Prevents Nitric Oxide-Induced Cytotoxicity and Endotoxin-Induced Death Circ. Res., April 14, 2006; 98(7): e60 - e65. [Abstract] [Full Text] [PDF]

				A. Yesilaltay, M. G. Morales, L. Amigo, S. Zanlungo, A. Rigotti, S. L. Karackattu, M. H. Donahee, K. F. Kozarsky, and M. Krieger Effects of Hepatic Expression of the High-Density Lipoprotein Receptor SR-BI on Lipoprotein Metabolism and Female Fertility Endocrinology, April 1, 2006; 147(4): 1577 - 1588. [Abstract] [Full Text] [PDF]

				M. Duong, H. L. Collins, W. Jin, I. Zanotti, E. Favari, and G. H. Rothblat Relative Contributions of ABCA1 and SR-BI to Cholesterol Efflux to Serum From Fibroblasts and Macrophages Arterioscler. Thromb. Vasc. Biol., March 1, 2006; 26(3): 541 - 547. [Abstract] [Full Text] [PDF]

				H. Yu, W. Zhang, P. G. Yancey, M. J. Koury, Y. Zhang, S. Fazio, and M. F. Linton Macrophage Apolipoprotein E Reduces Atherosclerosis and Prevents Premature Death in Apolipoprotein E and Scavenger Receptor-Class BI Double-Knockout Mice Arterioscler. Thromb. Vasc. Biol., January 1, 2006; 26(1): 150 - 156. [Abstract] [Full Text] [PDF]

				S. Fazio and M. F. Linton Interplay Between Apolipoprotein E and Scavenger Receptor Class B Type I Controls Coronary Atherosclerosis and Lifespan in the Mouse Circulation, June 28, 2005; 111(25): 3349 - 3351. [Full Text] [PDF]

				D. R. Greaves and S. Gordon Thematic review series: The Immune System and Atherogenesis. Recent insights into the biology of macrophage scavenger receptors J. Lipid Res., January 1, 2005; 46(1): 11 - 20. [Abstract] [Full Text] [PDF]

				A. J. Merched and L. Chan Absence of p21Waf1/Cip1/Sdi1 Modulates Macrophage Differentiation and Inflammatory Response and Protects Against Atherosclerosis Circulation, December 21, 2004; 110(25): 3830 - 3841. [Abstract] [Full Text] [PDF]

				S. Parathath, M. A. Connelly, R. A. Rieger, S. M. Klein, N. A. Abumrad, M. de la Llera-Moya, C. R. Iden, G. H. Rothblat, and D. L. Williams Changes in Plasma Membrane Properties and Phosphatidylcholine Subspecies of Insect Sf9 Cells Due to Expression of Scavenger Receptor Class B, Type I, and CD36 J. Biol. Chem., October 1, 2004; 279(40): 41310 - 41318. [Abstract] [Full Text] [PDF]

				M. Van Eck, I. S. T. Bos, R. B. Hildebrand, B. T. Van Rij, and T. J.C. Van Berkel Dual Role for Scavenger Receptor Class B, Type I on Bone Marrow-Derived Cells in Atherosclerotic Lesion Development Am. J. Pathol., September 1, 2004; 165(3): 785 - 794. [Abstract] [Full Text] [PDF]

				T. Fu, D. Mukhopadhyay, N. O. Davidson, and J. Borensztajn The Peroxisome Proliferator-activated Receptor {alpha} (PPAR{alpha}) Agonist Ciprofibrate Inhibits Apolipoprotein B mRNA Editing in Low Density Lipoprotein Receptor-deficient Mice: EFFECTS ON PLASMA LIPOPROTEINS AND THE DEVELOPMENT OF ATHEROSCLEROTIC LESIONS J. Biol. Chem., July 2, 2004; 279(27): 28662 - 28669. [Abstract] [Full Text] [PDF]

				T. J. F. Nieland, A. Chroni, M. L. Fitzgerald, Z. Maliga, V. I. Zannis, T. Kirchhausen, and M. Krieger Cross-inhibition of SR-BI- and ABCA1-mediated cholesterol transport by the small molecules BLT-4 and glyburide J. Lipid Res., July 1, 2004; 45(7): 1256 - 1265. [Abstract] [Full Text] [PDF]

				W. Zhang, P. G. Yancey, Y. R. Su, V. R. Babaev, Y. Zhang, S. Fazio, and M. F. Linton Inactivation of Macrophage Scavenger Receptor Class B Type I Promotes Atherosclerotic Lesion Development in Apolipoprotein E-Deficient Mice Circulation, November 4, 2003; 108(18): 2258 - 2263. [Abstract] [Full Text] [PDF]

				M. Cuchel and D. J. Rader Genetics of Increased HDL Cholesterol Levels: Insights Into the Relationship Between HDL Metabolism and Atherosclerosis Arterioscler. Thromb. Vasc. Biol., October 1, 2003; 23(10): 1710 - 1712. [Full Text] [PDF]

				B. L. Trigatti, M. Krieger, and A. Rigotti Influence of the HDL Receptor SR-BI on Lipoprotein Metabolism and Atherosclerosis Arterioscler. Thromb. Vasc. Biol., October 1, 2003; 23(10): 1732 - 1738. [Abstract] [Full Text] [PDF]

				O. L. Francone SR-BI: A New Player in an Old Game Arterioscler. Thromb. Vasc. Biol., September 1, 2003; 23(9): 1486 - 1487. [Full Text] [PDF]