This Article Full Text Full Text (PDF) 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 de Winther, M. P. J. Articles by Hofker, M. H. Search for Related Content PubMed PubMed Citation Articles by de Winther, M. P. J. Articles by Hofker, M. H.

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:290.)
© 2000 American Heart Association, Inc.

Brief Reviews

Macrophage Scavenger Receptor Class A

A Multifunctional Receptor in Atherosclerosis

Menno P. J. de Winther; Ko Willems van Dijk; Louis M. Havekes; Marten H. Hofker

From the Department of Human Genetics (M.P.J.d.W., K.W.v.D., M.H.H.), Leiden University Medical Center, and TNO-PG (L.M.H.), Gaubius Laboratory, Leiden, the Netherlands.

Correspondence to Dr Menno P.J. de Winther, Department of Human Genetics, Leiden University Medical Center, PO Box 9503, 2300 RA Leiden, Netherlands. E-mail mennow{at}ruly46.medfac.leidenuniv.nl

Abstract—In atherogenesis, elevated plasma levels of low density lipoprotein (LDL) lead to the chronic presence of LDL in the arterial wall. There, LDL is modified (eg, oxidized), and these modified lipoproteins activate endothelial cells, which attract circulating monocytes. These monocytes enter the vessel wall, differentiate into macrophages, and subject the modified lipoproteins to endocytosis through scavenger receptor pathways. This unrestricted uptake, which is not limited by intracellular cholesterol levels, eventually leads to the formation of lipid-filled foam cells, the initial step in atherosclerosis. Macrophage scavenger receptor class A (SRA) is thought to be one of the main receptors involved in foam cell formation, mediating the influx of lipids into the macrophages. In addition to this role in modified lipoprotein uptake by macrophages, the SRA has been shown to be important in the inflammatory response in host defense, cellular activation, adhesion, and cell-cell interaction. Given the importance of these processes in atherogenesis, these latter functions may prove to make the SRA a multifunctional player in the atherosclerotic process.

Key Words: inflammation • cardiovascular disease • modified lipoprotein • transgenic mouse

This article has been cited by other articles:

				A. Undurti, Y. Huang, J. A. Lupica, J. D. Smith, J. A. DiDonato, and S. L. Hazen Modification of High Density Lipoprotein by Myeloperoxidase Generates a Pro-inflammatory Particle J. Biol. Chem., November 6, 2009; 284(45): 30825 - 30835. [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]

				S. Kuchibhotla, D. Vanegas, D. J. Kennedy, E. Guy, G. Nimako, R. E. Morton, and M. Febbraio Absence of CD36 protects against atherosclerosis in ApoE knock-out mice with no additional protection provided by absence of scavenger receptor A I/II Cardiovasc Res, April 1, 2008; 78(1): 185 - 196. [Abstract] [Full Text] [PDF]

				H. Sano, M. Ishino, H. Kramer, T. Shimizu, H. Mitsuzawa, C. Nishitani, and Y. Kuroki The Microtubule-binding Protein Hook3 Interacts with a Cytoplasmic Domain of Scavenger Receptor A J. Biol. Chem., March 16, 2007; 282(11): 7973 - 7981. [Abstract] [Full Text] [PDF]

				H. K. Usui, K. Shikata, M. Sasaki, S. Okada, M. Matsuda, Y. Shikata, D. Ogawa, Y. Kido, R. Nagase, K. Yozai, et al. Macrophage Scavenger Receptor-A-Deficient Mice Are Resistant Against Diabetic Nephropathy Through Amelioration of Microinflammation Diabetes, February 1, 2007; 56(2): 363 - 372. [Abstract] [Full Text] [PDF]

				V. Amirbekian, M. J. Lipinski, K. C. Briley-Saebo, S. Amirbekian, J. G. S. Aguinaldo, D. B. Weinreb, E. Vucic, J. C. Frias, F. Hyafil, V. Mani, et al. Detecting and assessing macrophages in vivo to evaluate atherosclerosis noninvasively using molecular MRI PNAS, January 16, 2007; 104(3): 961 - 966. [Abstract] [Full Text] [PDF]

				E. Ikonen Mechanisms for cellular cholesterol transport: defects and human disease. Physiol Rev, October 1, 2006; 86(4): 1237 - 1261. [Abstract] [Full Text] [PDF]

				M. S. Arredouani, Z. Yang, A. Imrich, Y. Ning, G. Qin, and L. Kobzik The Macrophage Scavenger Receptor SR-AI/II and Lung Defense against Pneumococci and Particles Am. J. Respir. Cell Mol. Biol., October 1, 2006; 35(4): 474 - 478. [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]

				R. Stocker and J. F. Keaney Jr. Role of Oxidative Modifications in Atherosclerosis Physiol Rev, October 1, 2004; 84(4): 1381 - 1478. [Abstract] [Full Text] [PDF]

				J. Han, X. Zhou, T. Yokoyama, D. P. Hajjar, A. M. Gotto Jr, and A. C. Nicholson Pitavastatin Downregulates Expression of the Macrophage Type B Scavenger Receptor, CD36 Circulation, February 17, 2004; 109(6): 790 - 796. [Abstract] [Full Text] [PDF]

				M. K. C. Ng, S. Nakhla, A. Baoutina, W. Jessup, D. J. Handelsman, and D. S. Celermajer Dehydroepiandrosterone, an adrenalandrogen, increases human foam cell formation: a potentially pro-atherogenic effect J. Am. Coll. Cardiol., December 3, 2003; 42(11): 1967 - 1974. [Abstract] [Full Text] [PDF]

				G. Marsche, R. Zimmermann, S. Horiuchi, N. N. Tandon, W. Sattler, and E. Malle Class B Scavenger Receptors CD36 and SR-BI Are Receptors for Hypochlorite-modified Low Density Lipoprotein J. Biol. Chem., November 28, 2003; 278(48): 47562 - 47570. [Abstract] [Full Text] [PDF]

				K. A. Walton, X. Hsieh, N. Gharavi, S. Wang, G. Wang, M. Yeh, A. L. Cole, and J. A. Berliner Receptors Involved in the Oxidized 1-Palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine-mediated Synthesis of Interleukin-8: A ROLE FOR TOLL-LIKE RECEPTOR 4 AND A GLYCOSYLPHOSPHATIDYLINOSITOL-ANCHORED PROTEIN J. Biol. Chem., August 8, 2003; 278(32): 29661 - 29666. [Abstract] [Full Text] [PDF]

				G. N. Fredrikson, I. Soderberg, M. Lindholm, P. Dimayuga, K.-Y. Chyu, P. K. Shah, and J. Nilsson Inhibition of Atherosclerosis in ApoE-Null Mice by Immunization with ApoB-100 Peptide Sequences Arterioscler Thromb Vasc Biol, May 1, 2003; 23(5): 879 - 884. [Abstract] [Full Text] [PDF]

				F. C. W. Wu and A. von Eckardstein Androgens and Coronary Artery Disease Endocr. Rev., April 1, 2003; 24(2): 183 - 217. [Abstract] [Full Text] [PDF]

				J. Santiago-Garcia, T. Kodama, and R. E. Pitas The Class A Scavenger Receptor Binds to Proteoglycans and Mediates Adhesion of Macrophages to the Extracellular Matrix J. Biol. Chem., February 21, 2003; 278(9): 6942 - 6946. [Abstract] [Full Text] [PDF]

				S. R. Post, C. Gass, S. Rice, D. Nikolic, H. Crump, and G. R. Post Class A scavenger receptors mediate cell adhesion via activation of Gi/o and formation of focal adhesion complexes J. Lipid Res., November 1, 2002; 43(11): 1829 - 1836. [Abstract] [Full Text] [PDF]

				P. Lehtolainen, A. Taskinen, J. Laukkanen, K. J. Airenne, S. Heino, M. Lappalainen, K. Ojala, V. Marjomaki, J. F. Martin, M. S. Kulomaa, et al. Cloning and Characterization of Scavidin, a Fusion Protein for the Targeted Delivery of Biotinylated Molecules J. Biol. Chem., March 1, 2002; 277(10): 8545 - 8550. [Abstract] [Full Text] [PDF]