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Current Atherosclerosis Reports

, Volume 14, Issue 2, pp 150–159 | Cite as

Current Concepts of the Role of Oxidized LDL Receptors in Atherosclerosis

  • Tanu Goyal
  • Sona Mitra
  • Magomed Khaidakov
  • Xianwei Wang
  • Sandeep Singla
  • Zufeng Ding
  • Shijie Liu
  • Jawahar L. Mehta
Coronary Heart Disease (J Farmer, Section Editor)

Abstract

Atherosclerosis is characterized by accumulation of lipids and inflammatory cells in the arterial wall. Oxidized low-density lipoprotein (ox-LDL) plays important role in the genesis and progression of atheromatous plaque. Various scavenger receptors have been recognized in the past two decades that mediate uptake of ox-LDL leading to formation of foam cells. Inhibition of scavenger receptor A and CD36 has been shown to affect progression of atherosclerosis by decreasing foam cell formation. Lectin-type oxidized LDL receptor 1 (LOX-1) participates at various steps involved in the pathogenesis of atherosclerosis, and in experimental studies its blockade has been shown to affect the progression of atherosclerosis at multiple levels. In this review, we summarize the role of ox-LDL and scavenger receptors in the formation of atheroma with emphasis on effects of LOX-1 blockade.

Keywords

Atherosclerosis Scavenger receptors SRA-1 CD36 LOX1 

Notes

Disclosure

No conflicts of interest relevant to this article were reported.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Ross R. Atherosclerosis–an inflammatory disease. N Engl J Med. 1999;340(2):115–26.PubMedCrossRefGoogle Scholar
  2. 2.
    Harrison D, Griendling KK, Landmesser U, Hornig B, Drexler H. Role of oxidative stress in atherosclerosis. Am J Cardiol. 2003;91(3A):7A–11A.PubMedCrossRefGoogle Scholar
  3. 3.
    Libby P. Inflammation in atherosclerosis. Nature. 2002;420(6917):868–74.PubMedCrossRefGoogle Scholar
  4. 4.
    Davies MJ. Stability and instability: two faces of coronary atherosclerosis. The Paul Dudley white lecture 1995. Circulation. 1996;94(8):2013–20.PubMedGoogle Scholar
  5. 5.
    Virmani R, Burke AP, Farb A, Kolodgie FD. Pathology of the unstable plaque. Prog Cardiovasc Dis. 2002;44(5):349–56.PubMedCrossRefGoogle Scholar
  6. 6.
    Cai H, Harrison DG. Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ Res. 2000;87(10):840–4.PubMedGoogle Scholar
  7. 7.
    Kita T, Nagano Y, Yokode M, Ishii K, Kume N, Ooshima A, et al. Probucol prevents the progression of atherosclerosis in Watanabe heritable hyperlipidemic rabbit, an animal model for familial hypercholesterolemia. Proc Natl Acad Sci USA. 1987;84(16):5928–31.PubMedCrossRefGoogle Scholar
  8. 8.
    Cominacini L, Rigoni A, Pasini AF, Garbin U, Davoli A, Campagnola M, et al. The binding of oxidized low density lipoprotein [ox-LDL] to ox-LDL receptor-1 reduces the intracellular concentration of nitric oxide in endothelial cells through an increased production of superoxide. J Biol Chem. 2001;276(17):13750–5.PubMedGoogle Scholar
  9. 9.
    • Roy Chowdhury SK, Sangle GV, Xie X, Stelmack GL, Halayko AJ, Shen GX. Effects of extensively oxidized low-density lipoprotein on mitochondrial function and reactive oxygen species in porcine aortic endothelial cells. Am J Physiol Endocrinol Metab. 2010;298(1):E89–98. The findings in this article suggest that extensively oxidized LDL impairs enzymes in the mitochondrial respiratory chain and increases ROS in endothelial cells, which may contribute to vascular injury and pathogenesis of atherosclerosis. PubMedCrossRefGoogle Scholar
  10. 10.
    Hsieh CC, Yen MH, Yen CH, Lau YT. Oxidized low density lipoprotein induces apoptosis via generation of reactive oxygen species in vascular smooth muscle cells. Cardiovasc Res. 2001;49(1):135–45.PubMedCrossRefGoogle Scholar
  11. 11.
    • Bae YS, Lee JH, Choi SH, Kim S, Almazan F, Witztum JL, et al. Macrophages generate reactive oxygen species in response to minimally oxidized low-density lipoprotein: toll-like receptor 4- and spleen tyrosine kinase-dependent activation of NADPH oxidase 2. Circ Res. 2009;104(2):210–8. 21p following 218. This article states the pathway involved in the proatherogenic activation of macrophages via minimally oxidized LDL leading to generation of ROS increased expression of proinflammatory cytokines and migration of smooth muscle cells. PubMedCrossRefGoogle Scholar
  12. 12.
    Chen H, Li D, Saldeen T, Mehta JL. Transforming growth factor-beta[1] modulates oxidatively modified LDL-induced expression of adhesion molecules: role of LOX-1. Circ Res. 2001;89(12):1155–60.PubMedCrossRefGoogle Scholar
  13. 13.
    Martens JS, Lougheed M, Gomez-Munoz A, Steinbrecher UP. A modification of apolipoprotein B accounts for most of the induction of macrophage growth by oxidized low density lipoprotein. J Biol Chem. 1999;274(16):10903–10.PubMedCrossRefGoogle Scholar
  14. 14.
    Hu C, Dandapat A, Sun L, Khan JA, Liu Y, Hermonat PL, et al. Regulation of TGFbeta1-mediated collagen formation by LOX-1: studies based on forced overexpression of TGFbeta1 in wild-type and lox-1 knock-out mouse cardiac fibroblasts. J Biol Chem. 2008;283(16):10226–31.PubMedCrossRefGoogle Scholar
  15. 15.
    Chai YC, Binion DG, Macklis R, Chisolm III GM. Smooth muscle cell proliferation induced by oxidized LDL-borne lysophosphatidylcholine. Evidence for FGF-2 release from cells not extracellular matrix. Vascul Pharmacol. 2002;38(4):229–37.PubMedCrossRefGoogle Scholar
  16. 16.
    Chatterjee S, Ghosh N. Oxidized low density lipoprotein stimulates aortic smooth muscle cell proliferation. Glycobiology. 1996;6(3):303–11.PubMedCrossRefGoogle Scholar
  17. 17.
    • Chen KC, Wang YS, Hu CY, Chang WC, Liao YC, Dai CY, et al. OxLDL up-regulates microRNA-29b, leading to epigenetic modifications of MMP-2/MMP-9 genes: a novel mechanism for cardiovascular diseases. FASEB J. 2011;25(5):1718–1728. This article reports the role of ox-LDL in miRNA-mediated epigenetic regulation in atherosclerosis. It shows that ox-LDL upregulates miR-29b expression, leading to epigenetic modification in MMP-2/MMP-9 genes, which increased human aortic smooth muscle migration. PubMedCrossRefGoogle Scholar
  18. 18.
    Marwali MR, Hu CP, Mohandas B, Dandapat A, Deonikar P, Chen J, et al. Modulation of ADP-induced platelet activation by aspirin and Pravastatin: role of lectin-like oxidized low-density lipoprotein receptor-1, nitric oxide, oxidative stress, and inside-out integrin signaling. J Pharmacol Exp Ther. 2007;322(3):1324–32.PubMedCrossRefGoogle Scholar
  19. 19.
    Huang Y, Song L, Wu S, Fan F, Lopes-Virella MF. Oxidized LDL differentially regulates MMP-1 and TIMP-1 expression in vascular endothelial cells. Atherosclerosis. 2001;156(1):119–25.PubMedCrossRefGoogle Scholar
  20. 20.
    Shah PK, Falk E, Badimon JJ, Fernandez-Ortiz A, Mailhac A, Villareal-Levy G, et al. Human monocyte-derived macrophages induce collagen breakdown in fibrous caps of atherosclerotic plaques. Potential role of matrix-degrading metalloproteinases and implications for plaque rupture. Circulation. 1995;92(6):1565–9.PubMedGoogle Scholar
  21. 21.
    Ehara S, Ueda M, Naruko T, Haze K, Itoh A, Otsuka M, et al. Elevated levels of oxidized low density lipoprotein show a positive relationship with the severity of acute coronary syndromes. Circulation. 2001;103(15):1955–60.PubMedGoogle Scholar
  22. 22.
    Yamashita H, Ehara S, Yoshiyama M, Naruko T, Haze K, Shirai N, et al. Elevated plasma levels of oxidized low-density lipoprotein relate to the presence of angiographically detected complex and thrombotic coronary artery lesion morphology in patients with unstable angina. Circ J. 2007;71(5):681–7.PubMedCrossRefGoogle Scholar
  23. 23.
    • Santos AO, Fonseca FA, Fischer SM, Monteiro CM, Brandao SA, Povoa RM, et al. High circulating autoantibodies against human oxidized low-density lipoprotein are related to stable and lower titers to unstable clinical situation. Clin Chim Acta. 2009;406(1–2):113–118. This article explores the role of IgG anti–ox-LDL antibodies in relation to acute vascular events and reported that these antibodies could be protective in atherosclerosis as acute events are associated with decreased titres. PubMedCrossRefGoogle Scholar
  24. 24.
    Tsimikas S, Bergmark C, Beyer RW, Patel R, Pattison J, Miller E, et al. Temporal increases in plasma markers of oxidized low-density lipoprotein strongly reflect the presence of acute coronary syndromes. J Am Coll Cardiol. 2003;41(3):360–70.PubMedCrossRefGoogle Scholar
  25. 25.
    Pluddemann A, Neyen C, Gordon S. Macrophage scavenger receptors and host-derived ligands. Methods. 2007;43(3):207–17.PubMedCrossRefGoogle Scholar
  26. 26.
    de Beer MC, Zhao Z, Webb NR, van der Westhuyzen DR, de Villiers WJ. Lack of a direct role for macrosialin in oxidized LDL metabolism. J Lipid Res. 2003;44(4):674–85.PubMedCrossRefGoogle Scholar
  27. 27.
    Kunjathoor VV, Febbraio M, Podrez EA, Moore KJ, Andersson L, Koehn S, et al. Scavenger receptors class A-I/II and CD36 are the principal receptors responsible for the uptake of modified low density lipoprotein leading to lipid loading in macrophages. J Biol Chem. 2002;277(51):49982–8.PubMedCrossRefGoogle Scholar
  28. 28.
    Linton MF, Fazio S. Class A scavenger receptors, macrophages, and atherosclerosis. Curr Opin Lipidol. 2001;12(5):489–95.PubMedCrossRefGoogle Scholar
  29. 29.
    Suzuki H, Kurihara Y, Takeya M, Kamada N, Kataoka M, Jishage K, et al. A role for macrophage scavenger receptors in atherosclerosis and susceptibility to infection. Nature. 1997;386(6622):292–6.PubMedCrossRefGoogle Scholar
  30. 30.
    Babaev VR, Gleaves LA, Carter KJ, Suzuki H, Kodama T, Fazio S, et al. Reduced atherosclerotic lesions in mice deficient for total or macrophage-specific expression of scavenger receptor-A. Arterioscler Thromb Vasc Biol. 2000;20(12):2593–9.PubMedCrossRefGoogle Scholar
  31. 31.
    Sakaguchi H, Takeya M, Suzuki H, Hakamata H, Kodama T, Horiuchi S, et al. Role of macrophage scavenger receptors in diet-induced atherosclerosis in mice. Lab Invest. 1998;78(4):423–34.PubMedGoogle Scholar
  32. 32.
    de Winther MP, van Dijk KW, van Vlijmen BJ, Gijbels MJ, Heus JJ, Wijers ER, et al. Macrophage specific overexpression of the human macrophage scavenger receptor in transgenic mice, using a 180-kb yeast artificial chromosome, leads to enhanced foam cell formation of isolated peritoneal macrophages. Atherosclerosis. 1999;147(2):339–47.PubMedCrossRefGoogle Scholar
  33. 33.
    Nakata A, Nakagawa Y, Nishida M, Nozaki S, Miyagawa J, Nakagawa T, et al. CD36, a novel receptor for oxidized low-density lipoproteins, is highly expressed on lipid-laden macrophages in human atherosclerotic aorta. Arterioscler Thromb Vasc Biol. 1999;19(5):1333–9.PubMedCrossRefGoogle Scholar
  34. 34.
    Rahaman SO, Lennon DJ, Febbraio M, Podrez EA, Hazen SL, Silverstein RL. A CD36-dependent signaling cascade is necessary for macrophage foam cell formation. Cell Metab. 2006;4(3):211–21.PubMedCrossRefGoogle Scholar
  35. 35.
    Podrez EA, Febbraio M, Sheibani N, Schmitt D, Silverstein RL, Hajjar DP, et al. Macrophage scavenger receptor CD36 is the major receptor for LDL modified by monocyte-generated reactive nitrogen species. J Clin Invest. 2000;105(8):1095–108.PubMedCrossRefGoogle Scholar
  36. 36.
    Podrez EA, Schmitt D, Hoff HF, Hazen SL. Myeloperoxidase-generated reactive nitrogen species convert LDL into an atherogenic form in vitro. J Clin Invest. 1999;103(11):1547–60.PubMedCrossRefGoogle Scholar
  37. 37.
    Febbraio M, Podrez EA, Smith JD, Hajjar DP, Hazen SL, Hoff HF, et al. Targeted disruption of the class B scavenger receptor CD36 protects against atherosclerotic lesion development in mice. J Clin Invest. 2000;105(8):1049–56.PubMedCrossRefGoogle Scholar
  38. 38.
    Nozaki S, Kashiwagi H, Yamashita S, Nakagawa T, Kostner B, Tomiyama Y, et al. Reduced uptake of oxidized low density lipoproteins in monocyte-derived macrophages from CD36-deficient subjects. J Clin Invest. 1995;96(4):1859–65.PubMedCrossRefGoogle Scholar
  39. 39.
    Kuchibhotla S, Vanegas D, Kennedy DJ, Guy E, Nimako G, Morton RE, et al. 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. 2008;78(1):185–96.PubMedCrossRefGoogle Scholar
  40. 40.
    • Makinen PI, Lappalainen JP, Heinonen SE, Leppanen P, Lahteenvuo MT, Aarnio JV, et al. Silencing of either SR-A or CD36 reduces atherosclerosis in hyperlipidaemic mice and reveals reciprocal upregulation of these receptors. Cardiovasc Res. 2010;88(3):530–538. SR-A and CD36 play a role in foam cell formation via uptake of modified LDL, and silencing of each leads to decrease in atherosclerosis; however, silencing of both leads to reciprocal upregulation of these receptors, thus ameliorating the protective effects of their silencing. PubMedCrossRefGoogle Scholar
  41. 41.
    Moore KJ, Kunjathoor VV, Koehn SL, Manning JJ, Tseng AA, Silver JM, et al. Loss of receptor-mediated lipid uptake via scavenger receptor A or CD36 pathways does not ameliorate atherosclerosis in hyperlipidemic mice. J Clin Invest. 2005;115(8):2192–201.PubMedCrossRefGoogle Scholar
  42. 42.
    de Winther MP, Hofker MH. Scavenging new insights into atherogenesis. J Clin Invest. 2000;105(8):1039–41.PubMedCrossRefGoogle Scholar
  43. 43.
    Silverstein RL, Asch AS, Nachman RL. Glycoprotein IV mediates thrombospondin-dependent platelet-monocyte and platelet-U937 cell adhesion. J Clin Invest. 1989;84(2):546–52.PubMedCrossRefGoogle Scholar
  44. 44.
    Janabi M, Yamashita S, Hirano K, Matsumoto K, Sakai N, Hiraoka H, et al. Reduced adhesion of monocyte-derived macrophages from CD36-deficient patients to type I collagen. Biochem Biophys Res Commun. 2001;283(1):26–30.PubMedCrossRefGoogle Scholar
  45. 45.
    Fraser I, Hughes D, Gordon S. Divalent cation-independent macrophage adhesion inhibited by monoclonal antibody to murine scavenger receptor. Nature. 1993;364(6435):343–6.PubMedCrossRefGoogle Scholar
  46. 46.
    Jimenez B, Volpert OV, Crawford SE, Febbraio M, Silverstein RL, Bouck N. Signals leading to apoptosis-dependent inhibition of neovascularization by thrombospondin-1. Nat Med. 2000;6(1):41–8.PubMedCrossRefGoogle Scholar
  47. 47.
    Moulton KS, Heller E, Konerding MA, Flynn E, Palinski W, Folkman J. Angiogenesis inhibitors endostatin or TNP-470 reduce intimal neovascularization and plaque growth in apolipoprotein E-deficient mice. Circulation. 1999;99(13):1726–32.PubMedGoogle Scholar
  48. 48.
    Sawamura T, Kume N, Aoyama T, Moriwaki H, Hoshikawa H, Aiba Y, et al. An endothelial receptor for oxidized low-density lipoprotein. Nature. 1997;386(6620):73–7.PubMedCrossRefGoogle Scholar
  49. 49.
    Murase T, Kume N, Kataoka H, Minami M, Sawamura T, Masaki T, et al. Identification of soluble forms of lectin-like oxidized LDL receptor-1. Arterioscler Thromb Vasc Biol. 2000;20(3):715–20.PubMedCrossRefGoogle Scholar
  50. 50.
    Yoshida H, Kondratenko N, Green S, Steinberg D, Quehenberger O. Identification of the lectin-like receptor for oxidized low-density lipoprotein in human macrophages and its potential role as a scavenger receptor. Biochem J. 1998;334(Pt 1):9–13.PubMedGoogle Scholar
  51. 51.
    Chen M, Kakutani M, Naruko T, Ueda M, Narumiya S, Masaki T, et al. Activation-dependent surface expression of LOX-1 in human platelets. Biochem Biophys Res Commun. 2001;282(1):153–8.PubMedCrossRefGoogle Scholar
  52. 52.
    Kataoka H, Kume N, Miyamoto S, Minami M, Moriwaki H, Murase T, et al. Expression of lectinlike oxidized low-density lipoprotein receptor-1 in human atherosclerotic lesions. Circulation. 1999;99(24):3110–7.PubMedGoogle Scholar
  53. 53.
    Iwai-Kanai E, Hasegawa K, Sawamura T, Fujita M, Yanazume T, Toyokuni S, et al. Activation of lectin-like oxidized low-density lipoprotein receptor-1 induces apoptosis in cultured neonatal rat cardiac myocytes. Circulation. 2001;104(24):2948–54.PubMedCrossRefGoogle Scholar
  54. 54.
    Mehta JL, Li DY. Identification and autoregulation of receptor for OX-LDL in cultured human coronary artery endothelial cells. Biochem Biophys Res Commun. 1998;248(3):511–4.PubMedCrossRefGoogle Scholar
  55. 55.
    Li D, Mehta JL. Upregulation of endothelial receptor for oxidized LDL [LOX-1] by oxidized LDL and implications in apoptosis of human coronary artery endothelial cells: evidence from use of antisense LOX-1 mRNA and chemical inhibitors. Arterioscler Thromb Vasc Biol. 2000;20(4):1116–22.PubMedCrossRefGoogle Scholar
  56. 56.
    Jono T, Miyazaki A, Nagai R, Sawamura T, Kitamura T, Horiuchi S. Lectin-like oxidized low density lipoprotein receptor-1 [LOX-1] serves as an endothelial receptor for advanced glycation end products [AGE]. FEBS Lett. 2002;511(1–3):170–4.PubMedCrossRefGoogle Scholar
  57. 57.
    Li DY, Zhang YC, Philips MI, Sawamura T, Mehta JL. Upregulation of endothelial receptor for oxidized low-density lipoprotein [LOX-1] in cultured human coronary artery endothelial cells by angiotensin II type 1 receptor activation. Circ Res. 1999;84(9):1043–9.PubMedGoogle Scholar
  58. 58.
    Murase T, Kume N, Korenaga R, Ando J, Sawamura T, Masaki T, et al. Fluid shear stress transcriptionally induces lectin-like oxidized LDL receptor-1 in vascular endothelial cells. Circ Res. 1998;83(3):328–33.PubMedGoogle Scholar
  59. 59.
    Chen M, Nagase M, Fujita T, Narumiya S, Masaki T, Sawamura T. Diabetes enhances lectin-like oxidized LDL receptor-1 [LOX-1] expression in the vascular endothelium: possible role of LOX-1 ligand and AGE. Biochem Biophys Res Commun. 2001;287(4):962–8.PubMedCrossRefGoogle Scholar
  60. 60.
    Nagase M, Hirose S, Sawamura T, Masaki T, Fujita T. Enhanced expression of endothelial oxidized low-density lipoprotein receptor [LOX-1] in hypertensive rats. Biochem Biophys Res Commun. 1997;237(3):496–8.PubMedCrossRefGoogle Scholar
  61. 61.
    Chen M, Kakutani M, Minami M, Kataoka H, Kume N, Narumiya S, et al. Increased expression of lectin-like oxidized low density lipoprotein receptor-1 in initial atherosclerotic lesions of Watanabe heritable hyperlipidemic rabbits. Arterioscler Thromb Vasc Biol. 2000;20(4):1107–15.PubMedCrossRefGoogle Scholar
  62. 62.
    Hayashida K, Kume N, Murase T, Minami M, Nakagawa D, Inada T, et al. Serum soluble lectin-like oxidized low-density lipoprotein receptor-1 levels are elevated in acute coronary syndrome: a novel marker for early diagnosis. Circulation. 2005;112(6):812–8.PubMedCrossRefGoogle Scholar
  63. 63.
    •• Kume N, Mitsuoka H, Hayashida K, Tanaka M, Kita T. Soluble lectin-like oxidized low-density lipoprotein receptor-1 predicts prognosis after acute coronary syndrome--a pilot study. Circ J. 2010;74(7):1399–1404. Serum sLOX level is a biomarker of acute coronary syndrome. This article relates sLOX levels with prognosis after acute coronary syndromes. PubMedCrossRefGoogle Scholar
  64. 64.
    •• Kamezaki F, Yamashita K, Tasaki H, Kume N, Mitsuoka H, Kita T, et al. Serum soluble lectin-like oxidized low-density lipoprotein receptor-1 correlates with oxidative stress markers in stable coronary artery disease. Int J Cardiol. 2009;134(2):285–287. This article relates serum levels of sLOX-1 with oxidative stress level in vessel wall and severity of coronary artery disease, and thus highlights the potential role of sLOX-1 as a biomarker of oxidation stress and atherosclerosis. PubMedCrossRefGoogle Scholar
  65. 65.
    Li D, Yang B, Mehta JL. Ox-LDL induces apoptosis in human coronary artery endothelial cells: role of PKC, PTK, bcl-2, and Fas. Am J Physiol. 1998;275(2 Pt 2):H568–76.PubMedGoogle Scholar
  66. 66.
    Li D, Liu L, Chen H, Sawamura T, Ranganathan S, Mehta JL. LOX-1 mediates oxidized low-density lipoprotein-induced expression of matrix metalloproteinases in human coronary artery endothelial cells. Circulation. 2003;107(4):612–7.PubMedCrossRefGoogle Scholar
  67. 67.
    Li D, Mehta JL. Antisense to LOX-1 inhibits oxidized LDL-mediated upregulation of monocyte chemoattractant protein-1 and monocyte adhesion to human coronary artery endothelial cells. Circulation. 2000;101(25):2889–95.PubMedGoogle Scholar
  68. 68.
    Hu C, Dandapat A, Sun L, Chen J, Marwali MR, Romeo F, et al. LOX-1 deletion decreases collagen accumulation in atherosclerotic plaque in low-density lipoprotein receptor knockout mice fed a high-cholesterol diet. Cardiovasc Res. 2008;79(2):287–93.PubMedCrossRefGoogle Scholar
  69. 69.
    • Sun Y, Chen X. Ox-LDL-induced LOX-1 expression in vascular smooth muscle cells: role of reactive oxygen species. Fundam Clin Pharmacol. 2010. Ox-LDL leads to production of ROS and expression of LOX-1 on vascular smooth muscle cells via NF-κβ p65 expression and phosphorylation of JNK. Google Scholar
  70. 70.
    Mehta JL, Sanada N, Hu CP, Chen J, Dandapat A, Sugawara F, et al. Deletion of LOX-1 reduces atherogenesis in LDLR knockout mice fed high cholesterol diet. Circ Res. 2007;100(11):1634–42.PubMedCrossRefGoogle Scholar
  71. 71.
    •• Saito A, Shimizu H, Doi Y, Ishida T, Fujimura M, Inoue T, et al. Immunoliposomal drug-delivery system targeting lectin-like oxidized low-density lipoprotein receptor-1 for carotid plaque lesions in rats. J Neurosurg. 2011. The LOX-1 receptor can be potential target for prevention or cure of atherosclerosis.This article shows that liposomal drug delivery system targeting LOX-1 has decreased intimal thickness and MMP-9 in rat carotid plaque lesions. Google Scholar
  72. 72.
    Inoue K, Arai Y, Kurihara H, Kita T, Sawamura T. Overexpression of lectin-like oxidized low-density lipoprotein receptor-1 induces intramyocardial vasculopathy in apolipoprotein E-null mice. Circ Res. 2005;97(2):176–84.PubMedCrossRefGoogle Scholar
  73. 73.
    Ishigaki Y, Katagiri H, Gao J, Yamada T, Imai J, Uno K, et al. Impact of plasma oxidized low-density lipoprotein removal on atherosclerosis. Circulation. 2008;118(1):75–83.PubMedCrossRefGoogle Scholar
  74. 74.
    Periaortic and adventitial accumulation of macrophagesin LDLr knockout mice;Modulation by LOX1 deletion.abstract#342. SSCI proceedings 2008; 2008.Google Scholar
  75. 75.
    Boger RH, Bode-Boger SM, Frolich JC. The L-arginine-nitric oxide pathway: role in atherosclerosis and therapeutic implications. Atherosclerosis. 1996;127(1):1–11.PubMedCrossRefGoogle Scholar
  76. 76.
    Beckmann JS, Ye YZ, Anderson PG, Chen J, Accavitti MA, Tarpey MM, et al. Extensive nitration of protein tyrosines in human atherosclerosis detected by immunohistochemistry. Biol Chem Hoppe Seyler. 1994;375(2):81–8.PubMedCrossRefGoogle Scholar
  77. 77.
    • Gielis JF, Lin JY, Wingler K, Van Schil PE, Schmidt HH, Moens AL. Pathogenetic role of eNOS uncoupling in cardiopulmonary disorders. Free Radic Biol Med. 2011;50(7):765–776. Nitric oxide produced by eNOS dilates blood vessels and prevents atherosclerosis by maintaining endothelial function. Uncoupling of eNos generates ROS rather than NO, leading to atherosclerosis. Google Scholar
  78. 78.
    Eto H, Miyata M, Kume N, Minami M, Itabe H, Orihara K, et al. Expression of lectin-like oxidized LDL receptor-1 in smooth muscle cells after vascular injury. Biochem Biophys Res Commun. 2006;341(2):591–8.PubMedCrossRefGoogle Scholar
  79. 79.
    Kataoka H, Kume N, Miyamoto S, Minami M, Morimoto M, Hayashida K, et al. Oxidized LDL modulates Bax/Bcl-2 through the lectinlike Ox-LDL receptor-1 in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol. 2001;21(6):955–60.PubMedCrossRefGoogle Scholar
  80. 80.
    Yang X, Galeano NF, Szabolcs M, Sciacca RR, Cannon PJ. Oxidized low density lipoproteins alter macrophage lipid uptake, apoptosis, viability and nitric oxide synthesis. J Nutr. 1996;126(4 Suppl):1072S–5S.PubMedGoogle Scholar
  81. 81.
    Goldstein JL, Ho YK, Basu SK, Brown MS. Binding site on macrophages that mediates uptake and degradation of acetylated low density lipoprotein, producing massive cholesterol deposition. Proc Natl Acad Sci U S A. 1979;76(1):333–7.PubMedCrossRefGoogle Scholar
  82. 82.
    Febbraio M, Hajjar DP, Silverstein RL. CD36: a class B scavenger receptor involved in angiogenesis, atherosclerosis, inflammation, and lipid metabolism. J Clin Invest. 2001;108(6):785–91.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Tanu Goyal
    • 1
    • 2
  • Sona Mitra
    • 1
    • 2
  • Magomed Khaidakov
    • 1
    • 2
  • Xianwei Wang
    • 1
    • 2
  • Sandeep Singla
    • 1
    • 2
  • Zufeng Ding
    • 1
    • 2
  • Shijie Liu
    • 1
    • 2
  • Jawahar L. Mehta
    • 1
    • 2
  1. 1.University of Arkansas for Medical Sciences and Central Arkansas Veterans Health SystemLittle RockUSA
  2. 2.Cardiovascular DivisionUAMSLittle RockUSA

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