SciELO - Scientific Electronic Library Online

vol.33 número2Endothelial cell oxidative stress and signal transductionLipid peroxidation and antioxidants in hyperlipidemia and hypertension índice de autoresíndice de materiabúsqueda de artículos
Home Pagelista alfabética de revistas  

Servicios Personalizados




Links relacionados


Biological Research

versión impresa ISSN 0716-9760

Biol. Res. v.33 n.2 Santiago  2000 

Scavenger Receptors and Atherosclerosis


Departamento de Gastroenterología, Facultad de Medicina Pontificia Universidad Católica, Santiago, Chile


Scavenger receptors were discovered as cell surface proteins capable of binding and internalization of modified lipoproteins. These receptors exhibit a broad ligand binding specificity including potential physiological and pathophysiological ligands other than modified lipoproteins. Different classes of scavenger receptors have been identified, and their relevance in normal and pathological conditions is under investigation. Recent in vitro and in vivo studies strongly support the role of class A and class B scavenger receptors in lipid transport atherogenesis.

Key Words: atherosclerosis; cholesterol metabolism; lipoprotein; scavenger receptor; selective cholesterol uptake

Scavenger receptors are cell surface proteins that can bind and internalize modified lipoproteins, such as acetylated LDL and oxidized LDL. These receptors were initially described in cultured macrophages in which they mediate cholesterol uptake from modified lipoproteins determining the formation of lipid loaded macrophages closely resembling the foam cells present in atherosclerotic lesions (Brown & Goldstein, 1983). Because oxidized LDL seems to play a key role in foam cell formation during atherogenesis (Steinberg, 1997), macrophage scavenger receptor expression may be critical for the pathogenesis of atherosclerotic cardiovascular disease.

One of the most remarkable features of scavenger receptors is their broad ligand binding specificity including a variety of ligands such as chemically modified proteins (e.g., modified lipoproteins, maleylated bovine serum albumin), polysaccharides (e.g., dextran sulfate, fucoidin, carragheenan), polyribonucleotides (e.g., polyguanosine, polyinosine), anionic phospholipids (e.g., phosphatidylserine, phosphatidylinositol) and other anionic molecules (e.g., polyvinyl sulfate) (reviewed in Krieger & Herz, 1994).

The true (patho)physiological ligands for most scavenger receptors remain to be defined. In vitro and in vivo experiments have identified several non-lipoprotein scavenger receptor ligands that may be important for the understanding of the functional relevance of these cell surface receptors. Among these additional scavenger receptor ligands are bacterial surface components (e.g., lipopolysaccharide, lipoteichoic acid), beta-amyloid fibrils, advanced glycation end products, crocidolite asbestos, and oxidatively damaged, aged, and apoptotic cells (reviewed in Krieger & Herz, 1994; Kodama et al., 1996; Krieger, 1997; Greaves at al, 1998). The identification of these additional ligands is consistent with the proposal that scavenger receptors may play an important role in host defense through the recognition and clearance of endogenous and exogenous pathogenic substances (Krieger et al., 1993; Pearson, 1996; Krieger, 1997; Greaves at al, 1998). Thus, scavenger receptors are ideal candidates for the pattern recognition receptors involved in innate immunity (Medzhitov & Janeway, 1997), the non-adaptive immune response that evolved before the adaptive system involving the clonal B- and T-cell-mediated immune response.

The wide and complex ligand binding activity of scavenger receptors has suggested the existence of different classes of scavenger receptors. In fact, over the past decade, several classes of cDNAs have been cloned encoding different types of scavenger receptors which can also be found on cell types other than macrophages (Krieger, 1997; Greaves at al, 1998).

Both in vitro and in vivo experiments, as well as the analysis of class A and class B scavenger receptor gene-manipulated mouse models, have provided strong support for the role of these cell surface receptors in both physiological and pathophysiological conditions. This article will review the functional relevance of class A and class B scavenger receptors in lipid transport and atherosclerosis.

Class A Scavenger Receptors

The detailed molecular analysis of scavenger receptors began with the cDNA cloning of the macrophage scavenger receptor, which was called SR-A for scavenger receptors, class A (Kodama et al., 1990; Rohrer et al., 1990). SR-A are homotrimeric integral membrane proteins characterized by an elongated extracellular domain composed by an alpha-helical coiled coil region and a collagenous domain (reviewed in Krieger et al., 1993; Krieger & Herz, 1994; Kodama et al., 1996). The class A scavenger receptor gene generates two different forms of macrophage scavenger receptor proteins by alternative splicing; SR-A type I (SR-AI) has an additional carboxi-terminal cysteine-rich domain, which is not present in SR-A type II (SR-AII). The positively charged collagenous domain is critical for the ligand binding activity of SR-A. A structurally related macrophage scavenger receptor class A called MARCO (macrophage receptor with collagenous structure) shows a similar, but longer, collagenous domain without having the alpha-helical coiled coil region (Elomaa et al., 1995).

In addition to the ligand binding activity for modified lipoproteins, SR-A are involved in the binding and clearance of lipopolysaccharide in vivo and the binding of lipotheicoic acid and Gram positive bacteria such as Streptococcus pyogenes, Staphylococcus aureus, and Listeria monocytogenes (reviewed in Krieger et al., 1993; Krieger & Herz, 1994; Krieger et al., 1993; Kodama et al., 1996; Krieger, 1997; Greaves at al, 1998). SR-A also mediate the phagocytosis of apoptotic cells by macrophages (reviewed in Platt et al., 1999). In addition to its role in the uptake of modified lipoproteins and other polyanioinics, as well as in cell-cell interaction, SR-A has been shown to be relevant in cell adhesion, cell activation, and inflammatory response (reviewed in de Winther et al., 2000a).

Several lines of evidence provided indirect support for the role of SR-A during atherogenesis. First, SR-A bind and internalize with high affinity oxidized LDL (Kodama et al., 1990; Rohrer et al., 1990), a key modified lipoprotein for the pathogenesis of atherosclerosis (Steinberg, 1997). Second, the incubation of SR-A-transfected cultured cells with modified lipoproteins determines the formation of lipid-laden cells similar to the foam cells found in atherosclerotic plaques (Freeman, 1991). Third, SR-A expression has been detected in atherosclerotic lesions (Gough et al 1999). Based on these findings, SR-A was proposed to play a critical role in modified lipoprotein metabolism and atherosclerosis.

The generation of macrophage SR-A-deficient mice by gene targeting (Suzuki et al., 1997) has allowed a more direct analysis of the true functional activity of SR-A in lipid transport. The uptake and degradation of oxidized LDL and acetylated LDL by macrophages of SR-A knockout mice is significantly reduced, but not completely abolished, in comparison with macrophages from wild-type animals (Suzuki et al., 1997; Lougheed et al., 1997). However, plasma acetylated and oxidized LDL clearance was similar in SR-A knockout and wild-type mice (Ling et al., 1997). Taken together, these results show an important role of SR-A in modified LDL metabolism by macrophages in vitro but not in vivo, indicating the importance of alternative macrophage scavenger receptor(s) for the clearance of plasma modified LDL.

The role of SR-As in atherosclerosis was initially evaluated by studying the effect of SR-A deficiency on an apoE knockout mouse model, which spontaneously develops atherosclerotic plaques. The SR-A/apoE-deficient mice showed a 50% reduction in atherosclerotic lesion size compared to apoE knockout mice, indicating an influence of SR-A expression in the development of atherosclerosis in vivo (Suzuki et al., 1997). The role of SR-A during atherogenesis was also studied in SR-A/low density lipoprotein receptor (LDLR) double knockout mice after feeding an atherogenic diet (Sakaguchi et al., 1998). The atherosclerotic lesions were smaller in SR-A/LDLR deficient mice compared to LDLR single knockout mice. However, the presence of foam cells was still observed in atherosclerotic lesions of both SR-A/apoE and SR-A/LDLR knockout mice, suggesting that macrophage scavenger receptors other than SR-A also participate in atherogenesis. Furthermore, recent findings using a SR-A transgenic mouse model crossed to LDLR-deficient mice or apoE-3 Leiden transgenic mice have demonstrated an antiatherogenic role of SR-A (reviewed in de Winther et al., 2000b). Taken together, these studies indicate that SR-A plays important roles in atherogenesis, some of which are pro- and some of which are anti-atherogenic depending on the predominant local pathogenic factor(s) involved in atherosclerotic plaque formation in different animal models of the disease.

Scavenger Receptor SR-BI

The scavenger receptor class B, type I, SR-BI, was discovered during the study of a scavenger receptor activity different from that of SR-A (Acton et al., 1994). The SR-BI cDNA encodes a 509 amino acid protein, which contains one putative membrane-spanning hydrophobic domain on each end of the protein structure leaving a large extracellular region with a cysteine-rich carboxi-terminal half and multiple potential N-glycosylation sites. SR-BI is indeed a highly N-glycosylated 82 kDa protein, which is also modified by fatty acylation (Babitt et al., 1997).

As would be expected for a scavenger receptor, SR-BI binds modified lipoproteins (Acton et al., 1994), maleylated bovin serum albumin (Acton et al., 1994), anionic phospholipids (Rigotti et al., 1995) and apoptotic cells (Murao et al., 1997; Shiratsuchi et al., 1999; Svensson et al., 1999). Surprisingly, SR-BI also exhibits binding activity for native lipoproteins such as HDL, LDL and VLDL (Acton et al., 1994; Acton et al., 1996; Calvo et al., 1997). In fact, SR-BI is the first molecularly well-defined and functionally active cell surface HDL receptor capable of mediating selective HDL cholesterol uptake (Acton et al., 1996). Selective HDL cholesterol uptake is an important pathway for HDL metabolism in vivo involving cholesterol delivery from plasma HDL to the liver and steroidogenic tissues without HDL particle internalization and degradation (Glass et al., 1983).

A number of studies have provided indirect evidence for the relevance of SR-BI in HDL metabolism (reviewed in Rigotti et al., 1997; Krieger, 1999; Williams et al., 1999; Rigotti & Krieger, 1999). First, SR-BI binds HDL with high affinity facilitating selective and net cholesterol uptake from HDL to cells (Acton et al., 1996). Second, SR-BI is highly expressed in the liver and steroidogenic tissues (Acton et al., 1996; Landschulz et al., 1996), which are the main sites of selective HDL cholesterol uptake in vivo (Glass et al., 1983). SR-BI is also expressed in the yolk sac and placenta (Hatzopoulos et al., 1998; Wyne & Woollett, 1998), where it may facilitate the transfer of HDL cholesterol from the maternal circulation to the developing embryo. Third, SR-BI expression is coordinately regulated in steroidogenic cells in response to trophic hormones in vivo (Landschulz et al., 1996; Rigotti et al., 1997).

Interestingly, SR-BI expression levels also correlate with the rate of free cholesterol efflux to HDL in a wide variety of cell lines (Ji et al., 1997). Direct evidence for SR-BI function in cholesterol efflux was provided by studies in which SR-BI transfection into cultured cell stimulated free cholesterol efflux from cells into HDL (Jian et al., 1998). Therefore, SR-BI may indeed facilitate bidirectional cholesterol flux depending on the cholesterol gradient between HDL particles and the plasma membrane.

Recent SR-BI gene manipulation studies through adenovirus-mediated gene transfer, transgenesis, and gene targeting in mice have definitively established the relevance of SR-BI as a functional HDL receptor in vivo (reviewed in Krieger, 1999; Williams et al., 1999; Rigotti & Krieger, 1999; Williams et al., 1999; Trigatti et al., 2000; Trigatti & Rigotti, 2000) . Hepatic overexpression of SR-BI is associated with decreased plasma levels of HDL cholesterol (Kozarsky et al. , 1997; Wang et al., 1998; Ueda et al., 1999) and increased biliary cholesterol content (Kozarsky et al., 1997; Sehayek et al., 1998) suggesting that SR-BI mediates the hepatic uptake of HDL cholesterol to be further utilized for biliary secretion. In addition, SR-BI knockout mice and mice with attenuated hepatic expression of SR-BI exhibited elevated plasma HDL cholesterol concentrations (Rigotti et al., 1997; Varban et al., 1998), reduced selective HDL cholesterol clearance (Varban et al., 1998), decreased adrenal cholesterol content (Rigotti et al., 1997), and bile cholesterol concentration (Trigatti et al., 1999).

Because of its potential key activity in the initial (HDL-mediated cholesterol efflux from the arterial wall) as well as its established role in the last step (hepatic uptake of HDL cholesterol) of the reverse cholesterol transport pathway, SR-BI expression could be critical in mediating the well-known anti-atherogenic effect of HDL. Recent experiments using transgenic and knockout mice have addressed the effect of SR-BI expression levels on atherosclerosis (reviewed in Krieger & Kozarsky, 1999; Trigatti et al., 2000; Trigatti & Rigotti, 2000). SR-BI transgenesis in heterozygous LDL receptor-deficient mice fed with high fat/cholesterol/cholic acid diet (Arai et al., 1999), adenovirus-mediated SR-BI gene transfer in Western diet-fed mice (Kozarsky et al., 2000), and moderate SR-BI overexpression in apolipoprotein B transgenic mice (Ueda et al., 2000) resulted in marked reduction in atherosclerosis (Arai et al., 1999). In contrast, gene disruption of SR-BI in mice with an apoE-deficient background dramatically accelerated the onset of atherosclerosis (Trigatti et al., 1999), whereas attenuated SR-BI expression in LDLR-deficient mice exhibited increased atherosclerotic lesion size (Huszar et al., 2000). Taken together, these studies clearly demonstrated the antiatherogenic activity of SR-BI expression in the mouse.

The relevance of SR-BI for HDL metabolism in humans has not been established. Characterization of the human homologue of SR-BI has shown that the human version of this cell surface receptor is a functionally active HDL receptor in vitro (Calvo et al., 1997; Murao et al., 1997). SR-BI is also highly expressed in human liver and steroidogenic tissues (Cao et al., 1997). Therefore, SR-BI is a candidate cell surface HDL receptor for controlling HDL metabolism in humans but further research is required before its true relevance is definitively demonstrated. In particular, SR-BI gene and/or expression analyses in both populations, as well as families with inherited disorders in HDL metabolism, should provide critical insights on the physiological and pathophysiological significance of SR-BI in humans. In this regard, a recent population study has reported a significant association between human SR-BI gene polymorphisms and variations in plasma lipoprotein levels suggesting a role of SR-BI in human lipid metabolism (Acton, 1999). If SR-BI is a functionally relevant HDL receptor implicated in human atherosclerosis, it might offer a novel target for the prevention and/or treatment of coronary heart disease (Acton et al., 1999).


I acknowledge the support from the Research and Postgraduate Division of the Pontificia Universidad Católica de Chile and FONDECYT Grant #8990006 from the National Fund for Scientific and Technological Development (Chile).

Corresponding Author: Dr. Attilio Rigotti Departamento de Gastroenterología Facultad de Medicina,Pontificia Universidad Católica. Marcoleta 367, Santiago, Chile. Telephone: -2-6863832. Fax: 56-2-6397780. Email:

Received: January 30, 2000. Accepted: January 30, 2000


ACTON S, RIGOTTI A, LANDSCHULZ KT, XU S, HOBBS HH, KRIEGER M (1996) Identification of scavenger receptor SR-BI as a high density lipoprotein receptor. Science 271: 518-520         [ Links ]

ACTON SL, KOZARSKY KF, RIGOTTI A (1999) The HDL receptor SR-BI: a new therapeutic target for atherosclerosis? Mol Med Today 5: 518-524         [ Links ]

ACTON S, OSGOOD D, DONOGHUE M, CORELLA D, POCOVI M, CENARRO A, MOZAS P, KEILTY J, SQUAZZO S, WOOLF EA, ORDOVAS JM (1999) Association of polymorphisms at the SR-BI gene locus with plasma lipid levels and body mass index in a white population. Arterioscler Thromb Vasc Biol 19: 1734-1743         [ Links ]

ACTON SL, SCHERER PE, LODISH HF, KRIEGER M (1994) Expression cloning of SR-BI, a CD36-related class B scavenger receptor. J Biol Chem 269: 21003-21009         [ Links ]

ARAI, T, WANG N, BEZOUEVSKI M, WELCH C, TALL AR (1999) Decreased atherosclerosis in heterozygous low density lipoprotein receptor-deficient mice expressing the scavenger receptor BI transgene. J Biol Chem 274: 2366-2271         [ Links ]

BABITT J, TRIGATTI B, RIGOTTI A, SMART EJ, ANDERSON RG, XU S, KRIEGER M (1997) Murine SR-BI, a high density lipoprotein receptor that mediates selective lipid uptake, is N-glycosylated and fatty acylated and colocalizes with plasma membrane caveolae. J Biol Chem 272: 13242-13249         [ Links ]

BROWN MS, GOLDSTEIN JL (1983) Lipoprotein metabolism in the macrophage: implications for cholesterol deposition in atherosclerosis. Annu Rev Biochem 52: 223-261         [ Links ]

CALVO D, GOMEZ-CORONADO D, LASUNCION MA, VEGA MA (1997) CLA-1 is an 85-kD plasma membrane glycoprotein that acts as a high-affinity receptor for both native (HDL, LDL, and VLDL) and modified (OxLDL and AcLDL) lipoproteins. Arterioscler Thromb Vasc Biol 17: 2341-2349         [ Links ]

CAO G, GARCIA CK, WYNE KL, SCHULTZ RA, PARKER KL, HOBBS HH (1997) Structure and localization of the human gene encoding SR-BI/CLA-1. Evidence for transcriptional control by steroidogenic factor 1. J Biol Chem 272: 33068-33076         [ Links ]

DE WINTHER MP, VAN DIJK KW, HAVEKES LM, HOFKER MH (2000a) Macrophage scavenger receptor class A: A multifunctional receptor in atherosclerosis. Arterioscler Thromb Vasc Biol 20: 290-297 (In press)         [ Links ]

DE WINTHER MP, GIJBELS MJ, VAN DIJK KW, HAVEKES LM, HOFKER MH (2000b) Transgenic mouse models to study the role of the macrophage scavenger receptor class A in atherosclerosis. Int J Tissue React 22: 85-91 (In press)         [ Links ]

ELOMAA O, KANGAS M, SAHLBERG C, TUUKKANEN J, SORMUNEN R, LIAKKA A, THESLEFF I, KRAAL G, TRYGGVASON K (1995) Cloning of a novel bacteria-binding receptor structurally related to scavenger receptors and expressed in a subset of macrophages. Cell 80: 603-609         [ Links ]

FREEMAN M, EKKEL Y, ROHRER L, PENMAN M, FREEDMAN NJ, CHISOLM GM, KRIEGER M (1991) Expression of type I and type II bovine scavenger receptors in Chinese hamster ovary cells: lipid droplet accumulation and nonreciprocal cross competition by acetylated and oxidized low density lipoprotein. Proc Natl Acad Sci USA 88: 4931-4935         [ Links ]

GLASS C, PITTMAN RC, WEINSTEIN DB, STEINBERG D (1983) Dissociation of tissue uptake of cholesterol ester from that of apoprotein A-I of rat plasma high density lipoprotein: selective delivery of cholesterol ester to liver, adrenal, and gonad. Proc Natl Acad Sci USA 80: 5435-5439         [ Links ]

GOUGH PJ, GREAVES DR, SUZUKI H, HAKKINEN T, HILTUNEN MO, TURUNEN M, HERTTUALA SY, KODAMA T, GORDON S (1999) Analysis of macrophage scavenger receptor (SR-A) expression in human aortic atherosclerotic lesions. Arterioscler Thromb Vasc Biol 19: 461-471         [ Links ]

GREAVES DR, GOUGH PJ, GORDON S (1998) Recent progress in defining the role of scavenger receptors in lipid transport, atherosclerosis and host defence. Curr Opin Lipidol 9: 425-432         [ Links ]

HATZOPOULOS AK, RIGOTTI A, ROSENBERG RD, KRIEGER M (1998) Temporal and spatial pattern of expression of the HDL receptor SR-BI during murine embryogenesis. J Lipid Res 39: 495-508         [ Links ]

HUSZAR D, VARBAN ML, RINNINGER F, FEELEY R, ARAI T, FAIRCHILD-HUNTRESS V, DONOVAN MJ, TALL AR (2000) Increased LDL cholesterol and atherosclerosis in LDL receptor-deficient mice with attenuated expression of scavenger receptor B1. Arterioscler Thromb Vasc Biol 20: 1068-1073 (In press).         [ Links ]

JI Y, JIAN B, WANG N, SUN Y, MOYA ML, PHILLIPS MC, ROTHBLAT GH, SWANEY JB, TALL AR (1997) Scavenger receptor BI promotes high density lipoprotein-mediated cellular cholesterol efflux. J Biol Chem 272: 20982-20985         [ Links ]

JIAN B, DE LA LLERA-MOYA M, JI Y, WANG N, PHILLIPS MC, SWANEY JB, TALL AR, ROTHBLAT GH (1998) Scavenger receptor class B type I as a mediator of cellular cholesterol efflux to lipoproteins and phospholipid acceptors. J Biol Chem 273: 5599-5606         [ Links ]

KODAMA T, FREEMAN M, ROHRER L, ZABRECKY J, MATSUDAIRA P, KRIEGER M (1990) Type I macrophage scavenger receptor contains alpha-helical and collagen-like coiled coils. Nature 343: 531-535         [ Links ]

KODAMA T, DOI T, SUZUKI H, TAKAHASHI K, WADA Y, GORDON S (1996) Collagenous macrophage scavenger receptors. Curr Opin Lipidol 7: 287-291         [ Links ]

KOZARSKY KF, DONAHEE MH, RIGOTTI A, IQBAL SN, EDELMAN ER, KRIEGER M (1997) Overexpression of the HDL receptor SR-BI alters plasma HDL and bile cholesterol levels. Nature 387: 414-417         [ Links ]

KOZARSKY KF, DONAHEE MH, GLICK JM, KRIEGER M, RADER DJ (2000) Gene transfer and hepatic overexpression of the HDL receptor SR-BI reduces atherosclerosis in the cholesterol-fed LDL receptor-deficient mouse. Arterioscler Thromb Vasc Biol 20: 721-727 (In press)         [ Links ]

KRIEGER M (1997) The other side of scavenger receptors: pattern recognition for host defense. Curr Opin Lipidol 8: 275-280         [ Links ]

KRIEGER, M (1998) The «best» of cholesterols, the «worst» of cholesterols: a tale of two receptors. Proc Natl Acad Sci USA 95: 4077-4080         [ Links ]

KRIEGER M (1999) Charting the fate of the «good cholesterol»: identification and characterization of the high-density lipoprotein receptor SR-BI. Annu Rev Biochem. 68: 523-558.         [ Links ]

KRIEGER M, ACTON A, ASHKENAS J, PEARSON A, PENMAN M, RESNICK D (1993) Molecular flypaper, host defense, and atherosclerosis. J Biol Chem 268: 4569-4572         [ Links ]

KRIEGER M, HERZ J (1994) Structures and functions of multiligand lipoprotein receptors: macrophage scavenger receptors and LDL receptor-related protein (LRP). Annu Rev Biochem 63: 601-637         [ Links ]

KRIEGER M, KOZARSKY K (1999) Influence of the HDL receptor SR-BI on atherosclerosis. Curr Opin Lipidol. 10: 491-497         [ Links ]

LANDSCHULZ KT, PATHAK RK, RIGOTTI A, KRIEGER M, HOBBS HH (1996) Regulation of scavenger receptor, class B, type I, a high density lipoprotein receptor, in liver and steroidogenic tissues of the rat. J Clin Invest 98: 984-995         [ Links ]

LING W, LOUGHEED M, SUZUKI H, BUCHAN A, KODAMA T, STEINBRECHER UP (1997) Oxidized or acetylated low density lipoproteins are rapidly cleared by the liver in mice with disruption of the scavenger receptor class A type I/II gene. J Clin Invest 100: 244-252         [ Links ]

LOUGHEED M, LUM CM, LING W, SUZUKI H, KODAMA T, STEINBRECHER U (1997) High affinity saturable uptake of oxidized low density lipoprotein by macrophages from mice lacking the scavenger receptor class A type I/II. J Biol Chem 272: 12938-12944         [ Links ]

MEDZHITOV R, JANEWAY CA (1997) Innate immunity: the virtues of a nonclonal system of recognition. Cell 91: 295-298         [ Links ]

MURAO K, TERPSTRA V, GREEN SR, KONDRATENKO N, STEINBERG D, QUEHENBERGER O (1997) Characterization of CLA-1, a human homologue of rodent scavenger receptor BI, as a receptor for high density lipoprotein and apoptotic thymocytes. J Biol Chem 272: 17551-17557         [ Links ]

PEARSON AM (1996) Scavenger receptors in innate immunity. Curr Opin Immunol 8: 20-28         [ Links ]

PLATT N, DA SILVA RP, GORDON S (1999) Class A scavenger receptors and the phagocytosis of apoptotic cells. Immunol Lett 65: 15-19         [ Links ]

RIGOTTI A, TRIGATTI B, BABITT J, PENMAN M, XU S, KRIEGER M (1997) Scavenger receptor BI – a - a cell surface receptor for high density lipoprotein. Curr Opin Lipidol 8: 181-8         [ Links ]

RIGOTTI A, ACTON SL, KRIEGER M (1995) The class B scavenger receptors SR-BI and CD36 are receptors for anionic phospholipids. J Biol Chem 270:16221-16224         [ Links ]

RIGOTTI, A TRIGATTI BL, PENMAN M, RAYBURN H, HERZ J, KRIEGER M (1997) A targeted mutation in the murine gene encoding the high density lipoprotein (HDL) receptor scavenger receptor class B type I reveals its key role in HDL metabolism. Proc Natl Acad Sci USA 94: 12610-12615         [ Links ]

RIGOTTI A, KRIEGER M (1999) Getting a handle on «good» cholesterol with the high-density lipoprotein receptor. N Engl J Med. 341: 2011-2013.         [ Links ]

ROHRER L, FREEMAN M, KODAMA T, PENMAN M, KRIEGER M (1990) Coiled-coil fibrous domains mediate ligand binding by macrophage scavenger receptor type II. Nature 343: 570-572         [ Links ]

SAKAGUCHI H, TAKEYA M, SUZUKI H, HAKAMATA H, KODAMA T, HORIUCHI S, GORDON S, VAN DER LAAN LJ, KRAAL G, ISHIBASHI S, KITAMURA N, TAKAHASHI K (1998) Role of macrophage scavenger receptors in diet-induced atherosclerosis in mice. Lab Invest 78: 423-434         [ Links ]

SEHAYEK E, ONO JG, SHEFER S, NGUYEN LB, WANG N, BATTA AK, SALEN G, SMITH JD, TALL AR, BRESLOW JL (1998) Biliary cholesterol excretion: A novel mechanism that regulates dietary cholesterol absorption. Proc Natl Acad Sci USA 95: 10194-10199         [ Links ]

SHIRATSUCHI A, KAWASAKI Y, IKEMOTO M, ARAI H, NAKANISHI Y (1999) Role of class B scavenger receptor type I in phagocytosis of apoptotic rat spermatogenic cells by Sertoli cells. J Biol Chem 274: 5901-5908         [ Links ]

STEINBERG D (1997) Low density lipoprotein oxidation and its pathobiological significance. J Biol Chem 272: 20963-20966         [ Links ]

SUZUKI H, KURIHARA Y, TAKEYA M, KAMADA N, KATAOKA M, JISHAGE K, UEDA O, SAKAGUCHI H, HIGASHI T, SUZUKI T, TAKASHIMA Y, KAWABE Y, CYNSHI O, WADA Y, HONDA M, KURIHARA H, ABURATANI H, DOI T, MATSUMOTO A, AZUMA S, NODA T, TOYODA Y, ITAKURA H, YAZAKI Y, KODAMA T (1997) A role for macrophage scavenger receptors in atherosclerosis and susceptibility to infection. Nature 386: 292-296         [ Links ]

SVENSSON PA, JOHNSON MS, LING C, CARLSSON LM, BILLIG H, CARLSSON B (1999) Scavenger receptor class B type I in the rat ovary: possible role in high density lipoprotein cholesterol uptake and in the recognition of apoptotic granulosa cells. Endocrinology 140: 2494-2500         [ Links ]

TRIGATTI B, RIGOTTI A (2000) Scavenger receptor class B type I (SR-BI) and high-density lipoprotein metabolism: recent lessons from genetically manipulated mice. Int J Tissue React 22: 29-37 (In press)         [ Links ]

TRIGATTI B, RAYBURN H, VIÑALS M, BRAUN A, MIETTINEN H, PENMAN M, HERTZ M, SCHRENZEL M, AMIGO L, RIGOTTI A, KRIEGER M (1999) Influence of the HDL receptor SR-BI on reproductive and cardiovascular pathophysiology. Proc Natl Acad Sci U S A 96: 9322-9327         [ Links ]

TRIGATTI B, RIGOTTI A, KRIEGER M (2000) The role of the high-density lipoprotein receptor SR-BI in cholesterol metabolism. Curr Opin Lipidol 11: 123-31 (In press)         [ Links ]

UEDA Y ROYER L, GONG E, ZHANG J, COOPER PN, FRANCONE O, RUBIN EM (1999) Lower plasma levels and accelerated clearance of high density lipoprotein (HDL) and non-HDL cholesterol in scavenger receptor class B type I transgenic mice. J Biol Chem 274: 7165-7171         [ Links ]

UEDA Y, GONG E, ROYER L, COOPER PN, FRANCONE OL, RUBIN EM (2000) Relationship between expression levels and atherogenesis in scavenger receptor Class B, type I transgenics. J Biol Chem 275: 20368-20373 (In press)         [ Links ]

VARBAN ML, RINNINGER F, WANG N, FAIRCHILD-HUNTRESS V, DUNMORE JH, FANG Q, GOSSELIN ML, DIXON KL, DEEDS JD, ACTON SL, TALL AR, HUSZAR D (1998) Targeted mutation reveals a central role for SR-BI in hepatic selective uptake of high density lipoprotein cholesterol. Proc Natl Acad Sci USA 95: 4619-4624         [ Links ]

WANG N, ARAI T, JI Y, RINNINGER F, TALL AR (1998) Liver-specific overexpression of scavenger receptor BI decreases levels of very low density lipoprotein ApoB, low density lipoprotein ApoB, and high density lipoprotein in transgenic mice. J Biol Chem 273: 32920-32926         [ Links ]

WILLIAMS DL, CONNELLY MA, TEMEL RE, SWARNAKAR S, PHILLIPS MC, DE LA LLERA-MOYA M, ROTHBLAT GH (1999) Scavenger receptor BI and cholesterol trafficking. Curr Opin Lipidol 10: 329-339         [ Links ]

WYNE KL, WOOLLETT LA (1998) Transport of maternal LDL and HDL to the fetal membranes and placenta of the Golden Syrian hamster is mediated by receptor-dependent and receptor-independent processes. J Lipid Res 39: 518-530         [ Links ]

Creative Commons License Todo el contenido de esta revista, excepto dónde está identificado, está bajo una Licencia Creative Commons