Published online before print October 27, 2003, doi: 10.1161/01.CIR.0000093189.97429.9D
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2003;108:2258.)
© 2003 American Heart Association, Inc.
Basic Science Reports |
Inactivation of Macrophage Scavenger Receptor Class B Type I Promotes Atherosclerotic Lesion Development in Apolipoprotein E–Deficient Mice
From the Atherosclerosis Research Unit, Division of Cardiovascular Medicine, Departments of Medicine (W.Z., P.G.Y., Y.R.S., V.B., Y.Z., S.F., M.F.L.), Pharmacology (M.F.L.), and Pathology (S.F.), Vanderbilt University Medical Center, Nashville, Tenn.
Correspondence to MacRae F. Linton or Sergio Fazio, 383 PRB, 2220 Pierce Ave, Vanderbilt University Medical Center, Nashville, TN 37232-6300. E-mail macrae.linton{at}vanderbilt.edu or sergio.fazio@vanderbilt.edu
Received April 4, 2003; revision received July 9, 2003; accepted July 11, 2003.
Background— Scavenger receptor class B type I (SR-BI) is expressed in macrophages, where it has been proposed to facilitate cholesterol efflux. However, direct evidence that the expression of macrophage SR-BI is protective against atherosclerosis is lacking. In this study, we examined the in vivo role of macrophage SR-BI in atherosclerotic lesion development in the apolipoprotein (apo) E–deficient mouse model.
Methods and Results— ApoE-deficient mice with (n=16) or without (n=15) expression of macrophage SR-BI were created by transplanting lethally irradiated apoE-deficient mice with bone marrow cells collected from SR-BI-/- apoE-/- mice or SR-BI+/+ apoE-/- mice. The recipient mice were fed a chow diet for 12 weeks after transplantation for analysis of atherosclerosis. Quantification of macrophage SR-BI mRNA by real-time reverse transcription–polymerase chain reaction indicated successful engraftment of donor bone marrow and inactivation of macrophage SR-BI in recipient mice reconstituted with SR-BI-/- apoE-/- bone marrow. There were no significant differences in plasma lipid levels, lipoprotein distributions, and HDL subpopulations between the 2 groups. Analysis of the proximal aorta demonstrated an 86% increase in mean atherosclerotic lesion area in SR-BI-/- apoE-/- 
apoE-/- mice compared with SR-BI+/+ apoE-/- apoE-/- mice (109.50±18.08 versus 58.75±9.58x103 µm2; mean±SEM, P=0.017). No difference in cholesterol efflux from SR-BI+/+ apoE-/- or SR-BI-/- apoE-/- macrophages to HDL or apoA-I discs was detected.
Conclusions— Expression of macrophage SR-BI protects mice against atherosclerotic lesion development in apoE-deficient mice in vivo without influencing plasma lipids, HDL subpopulations, or cholesterol efflux. Thus, macrophage SR-BI plays an antiatherogenic role in vivo, providing a new therapeutic target for the design of strategies to prevent and treat atherosclerosis.
Key Words: macrophages • receptors • cholesterol • atherosclerosis
This article has been cited by other articles:
 |
|
 |
|
  Y. R. Su, J. L. Blakemore, Y. Zhang, M. F. Linton, and S. Fazio Lentiviral Transduction of ApoAI Into Hematopoietic Progenitor Cells and Macrophages: Applications to Cell Therapy of Atherosclerosis Arterioscler. Thromb. Vasc. Biol., August 1, 2008; 28(8): 1439 - 1446. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Valiyaveettil, N. Kar, M. Z. Ashraf, T. V. Byzova, M. Febbraio, and E. A. Podrez Oxidized high-density lipoprotein inhibits platelet activation and aggregation via scavenger receptor BI Blood, February 15, 2008; 111(4): 1962 - 1971. [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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
H. Berrougui, M. Isabelle, M. Cloutier, G. Grenier, and A. Khalil Age-related impairment of HDL-mediated cholesterol efflux J. Lipid Res., February 1, 2007; 48(2): 328 - 336. [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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
R. E. Moore, M. Navab, J. S. Millar, F. Zimetti, S. Hama, G. H. Rothblat, and D. J. Rader Increased Atherosclerosis in Mice Lacking Apolipoprotein A-I Attributable to Both Impaired Reverse Cholesterol Transport and Increased Inflammation Circ. Res., October 14, 2005; 97(8): 763 - 771. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Daugherty, N. R. Webb, D. L. Rateri, and V. L. King Thematic review series: The Immune System and Atherogenesis. Cytokine regulation of macrophage functions in atherogenesis J. Lipid Res., September 1, 2005; 46(9): 1812 - 1822. [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. Lan and D. L. Silver Fenofibrate Induces a Novel Degradation Pathway for Scavenger Receptor B-I Independent of PDZK1 J. Biol. Chem., June 17, 2005; 280(24): 23390 - 23396. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. R. Su, D. E. Dove, A. S. Major, A. H. Hasty, B. Boone, M. F. Linton, and S. Fazio Reduced ABCA1-Mediated Cholesterol Efflux and Accelerated Atherosclerosis in Apolipoprotein E-Deficient Mice Lacking Macrophage-Derived ACAT1 Circulation, May 10, 2005; 111(18): 2373 - 2381. [Abstract] [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]
|
|
|
|
 |
|
 N. Wang, D. Lan, W. Chen, F. Matsuura, and A. R. Tall ATP-binding cassette transporters G1 and G4 mediate cellular cholesterol efflux to high-density lipoproteins PNAS, June 29, 2004; 101(26): 9774 - 9779. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. S. Meir and E. Leitersdorf Atherosclerosis in the Apolipoprotein E-Deficient Mouse: A Decade of Progress Arterioscler. Thromb. Vasc. Biol., June 1, 2004; 24(6): 1006 - 1014. [Abstract] [Full Text] [PDF]
|
|