Published online before print May 25, 2006, doi: 10.1161/01.ATV.0000229218.97976.43
© 2006 American Heart Association, Inc.
Brief Reviews |
Scavenger Receptors in Atherosclerosis
Beyond Lipid Uptake
From the Lipid Metabolism Unit, Massachusetts General Hospital, Harvard Medical School, Boston.
Correspondence to Kathryn J. Moore, PhD, Lipid Metabolism Unit, GRJ1328, Massachusetts General Hospital, 55 Fruit St, Boston, MA 02114. E-mail kmoore{at}molbio.mgh.harvard.edu
Atherosclerotic vascular disease arises as a consequence of the deposition and retention of serum lipoproteins in the artery wall. Macrophages in lesions have been shown to express 
6 structurally different scavenger receptors for uptake of modified forms of low-density lipoproteins (LDLs) that promote the cellular accumulation of cholesterol. Because cholesterol-laden macrophage foam cells are the primary component of the fatty streak, the earliest atherosclerotic lesion, lipid uptake by these pathways has long been considered a requisite and initiating event in the pathogenesis of atherosclerosis. Although the removal of proinflammatory modified LDLs from the artery wall via scavenger receptors would seem beneficial, the pathways distal to scavenger receptor uptake that metabolize the modified lipoproteins appear to become overwhelmed, leading to the accumulation of cholesterol-laden macrophages and establishment of a chronic inflammatory setting. These observations have led to the current dogma concerning scavenger receptors, which is that they are proatherogenic molecules. However, recent studies suggest that the effects of scavenger receptors on atherogenesis may be more complex. In addition to modified lipoprotein uptake, these proteins are now known to regulate apoptotic cell clearance, initiate signal transduction, and serve as pattern recognition receptors for pathogens, activities that may contribute both to proinflammatory and anti-inflammatory forces regulating atherogenesis. In this review, we focus on recent advances in our knowledge of scavenger receptor regulation and signal transduction, their roles in sterile inflammation and infection, and the potential impact of these pathways in regulating the balance of lipid accumulation and inflammation in the artery wall.
Atherosclerosis arises from the deposition and retention of serum lipoproteins in the artery wall. Macrophage scavenger receptors bind modified lipoproteins and promote cellular cholesterol accumulation in the artery wall. This review focuses on recent advances in scavenger receptor regulation and signal transduction, and highlights their roles in lipid accumulation and inflammation.
This article has been cited by other articles:
 |
|
 |
|
  K. Rayner, Y.-X. Chen, M. McNulty, T. Simard, X. Zhao, D. J. Wells, J. de Belleroche, and E. R. O'Brien Extracellular Release of the Atheroprotective Heat Shock Protein 27 Is Mediated by Estrogen and Competitively Inhibits acLDL Binding to Scavenger Receptor-A Circ. Res., July 18, 2008; 103(2): 133 - 141. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Gleissner, J. M. Sanders, J. Nadler, and K. Ley Upregulation of Aldose Reductase During Foam Cell Formation as Possible Link Among Diabetes, Hyperlipidemia, and Atherosclerosis Arterioscler. Thromb. Vasc. Biol., June 1, 2008; 28(6): 1137 - 1143. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Malarstig, S. Sigurdsson, P. Eriksson, G. Paulsson-Berne, U. Hedin, L. Wallentin, A. Siegbahn, A. Hamsten, and A.-C. Syvanen Variants of the Interferon Regulatory Factor 5 Gene Regulate Expression of IRF5 mRNA in Atherosclerotic Tissue But Are Not Associated With Myocardial Infarction Arterioscler. Thromb. Vasc. Biol., May 1, 2008; 28(5): 975 - 982. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Kim, A. T. Tolhurst, L. Y. Qin, X.-Y. Chen, M. Febbraio, and S. Cho CD36/Fatty Acid Translocase, An Inflammatory Mediator, Is Involved in Hyperlipidemia-Induced Exacerbation in Ischemic Brain Injury J. Neurosci., April 30, 2008; 28(18): 4661 - 4670. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Siegel-Axel, K. Daub, P. Seizer, S. Lindemann, and M. Gawaz Platelet lipoprotein interplay: trigger of foam cell formation and driver of atherosclerosis Cardiovasc Res, April 1, 2008; 78(1): 8 - 17. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Greenberg, X.-M. Li, B. G. Gugiu, X. Gu, J. Qin, R. G. Salomon, and S. L. Hazen The Lipid Whisker Model of the Structure of Oxidized Cell Membranes J. Biol. Chem., January 25, 2008; 283(4): 2385 - 2396. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. V. Limmon, M. Arredouani, K. L. McCann, R. A. C. Minor, L. Kobzik, and F. Imani Scavenger receptor class-A is a novel cell surface receptor for double-stranded RNA FASEB J, January 1, 2008; 22(1): 159 - 167. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Sun, B. B. Boyanovsky, M. A. Connelly, P. Shridas, D. R. van der Westhuyzen, and N. R. Webb Distinct mechanisms for OxLDL uptake and cellular trafficking by class B scavenger receptors CD36 and SR-BI J. Lipid Res., December 1, 2007; 48(12): 2560 - 2570. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Jagavelu, U. J.F. Tietge, M. Gaestel, H. Drexler, B. Schieffer, and U. Bavendiek Systemic Deficiency of the MAP Kinase Activated Protein Kinase 2 Reduces Atherosclerosis in Hypercholesterolemic Mice Circ. Res., November 26, 2007; 101(11): 1104 - 1112. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Collot-Teixeira, J. Martin, C. McDermott-Roe, R. Poston, and J. L. McGregor CD36 and macrophages in atherosclerosis Cardiovasc Res, August 1, 2007; 75(3): 468 - 477. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Gleissner, N. Leitinger, and K. Ley Effects of Native and Modified Low-Density Lipoproteins on Monocyte Recruitment in Atherosclerosis Hypertension, August 1, 2007; 50(2): 276 - 283. [Full Text] [PDF]
|
|
|
|
 |
|
 J. Maleszewski, J. Lu, K. Fox-Talbot, and M. K. Halushka Robust Immunohistochemical Staining of Several Classes of Proteins in Tissues Subjected to Autolysis J. Histochem. Cytochem., June 1, 2007; 55(6): 597 - 606. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Ohwaki, H. Bujo, M. Jiang, H. Yamazaki, W. J. Schneider, and Y. Saito A Secreted Soluble Form of LR11, Specifically Expressed in Intimal Smooth Muscle Cells, Accelerates Formation of Lipid-Laden Macrophages Arterioscler. Thromb. Vasc. Biol., May 1, 2007; 27(5): 1050 - 1056. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. C.H. Kwan, F. Kronenberg, S. Beddhu, and A. K. Cheung Lipoprotein Metabolism and Lipid Management in Chronic Kidney Disease J. Am. Soc. Nephrol., April 1, 2007; 18(4): 1246 - 1261. [Full Text] [PDF]
|
|
|
|
|
|
M.-D. Wang, R. S. Kiss, V. Franklin, H. M. McBride, S. C. Whitman, and Y. L. Marcel Different cellular traffic of LDL-cholesterol and acetylated LDL-cholesterol leads to distinct reverse cholesterol transport pathways J. Lipid Res., March 1, 2007; 48(3): 633 - 645. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. W. Parks, A. J. Lusis, and J. H.S. Kabarowski Loss of the Lysophosphatidylcholine Effector, G2A, Ameliorates Aortic Atherosclerosis in Low-Density Lipoprotein Receptor Knockout Mice Arterioscler. Thromb. Vasc. Biol., December 1, 2006; 26(12): 2703 - 2709. [Abstract] [Full Text] [PDF]
|
|