Treating atherosclerosis: The potential of Toll-like receptors as therapeutic targets

Expert Review of Cardiovascular Therapy

Volumn 8, Issue 11, 2010, Pages 1619-1635

  Cole, Jennifer E ^a   Mitra, Anuja T ^a   Monaco, Claudia ^a  

^a IMPERIAL COLLEGE LONDON   (United Kingdom)

Author keywords

atherosclerosis; inflammation; therapeutics; Toll like receptor

Indexed keywords

APOLIPOPROTEIN C3; BACTERIUM LIPOPOLYSACCHARIDE; ERITORAN; FIBRINOGEN; FIBRONECTIN; FLAGELLIN; HEAT SHOCK PROTEIN; HYALURONIC ACID; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; LIPOPROTEIN; LIPOTEICHOIC ACID; LOW DENSITY LIPOPROTEIN; MICRORNA; MONOCLONAL ANTIBODY; MYELOID DIFFERENTIATION FACTOR 88; OPN 305; PEPTIDOGLYCAN; PLACEBO; TENASCIN; TOLL LIKE RECEPTOR; TOLL LIKE RECEPTOR 1; TOLL LIKE RECEPTOR 2; TOLL LIKE RECEPTOR 3; TOLL LIKE RECEPTOR 4; TOLL LIKE RECEPTOR 6; TOLL LIKE RECEPTOR 7; TOLL LIKE RECEPTOR 8; TOLL LIKE RECEPTOR 9; TUMOR NECROSIS FACTOR ANTIBODY; UNCLASSIFIED DRUG; ZYMOSAN;

ATHEROGENESIS; ATHEROMA; ATHEROSCLEROSIS; CLINICAL TRIAL; FOAM CELL; HUMAN; INFLAMMATORY DISEASE; LEUKOCYTE ACTIVATION; LEUKOCYTE MIGRATION; NONHUMAN; PROTEIN EXPRESSION; PROTEIN FUNCTION; RECEPTOR BLOCKING; REVIEW; RHEUMATOID ARTHRITIS; SIGNAL TRANSDUCTION;

ATHEROSCLEROSIS; CYTOKINES; HUMANS; INFLAMMATION; MOLECULAR TARGETED THERAPY; SIGNAL TRANSDUCTION; TOLL-LIKE RECEPTORS;

EID: 78649344532     PISSN: 14779072     EISSN: 17448344     Source Type: Journal    
DOI: 10.1586/erc.10.149     Document Type: Review

References (214)

1. Lopez AD, Mathers CD, Ezzati M, Jamison DT, Murray CJ. Global and regional burden of disease and risk factors, 2001: systematic ana lysis of population health data. Lancet 367(9524), 1747-1757 (2006).
2. Caro CG. Discovery of the role of wall shear in atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 29(2), 158-161 (2009).
3. Furnkranz A, Schober A, Bochkov VN et al. Oxidized phospholipids trigger atherogenic infammation in murine arteries. Arterioscler. Thromb. Vasc. Biol. 25(3), 633-638 (2005).
4. Iiyama K, Hajra L, Iiyama M et al. Patterns of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 expression in rabbit and mouse atherosclerotic lesions and at sites predisposed to lesion formation. Circ. Res. 85(2), 199-207 (1999).
5. Nakashima Y, Raines EW, Plump AS, Breslow JL, Ross R. Upregulation of VCAM-1 and ICAM-1 at atherosclerosis-prone sites on the endothelium in the ApoE-defcient mouse. Arterioscler. Thromb. Vasc. Biol. 18(5), 842-851 (1998).
6. Geissmann F, Jung S, Littman DR. Blood monocytes consist of two principal subsets with distinct migratory properties. Immunity 19(1), 71-82 (2003).
7. Gordon S, Taylor P. Monocyte and macrophage heterogeneity. Nat. Rev. Immunol. 5(12), 953-964 (2005).
8. Tacke F, Randolph G. Migratory fate and differentiation of blood monocyte subsets. Immunobiology 211(6-8), 609-618 (2006).
9. (+) blood monocytes. Eur. J. Immunol. 31(1), 48-56 (2001).
10. Tacke F, Alvarez D, Kaplan T et al. Monocyte subsets differentially employ CCR2, CCR5, and CX3CR1 to accumulate within atherosclerotic plaques. J. Clin. Invest. 117(1), 185-194 (2007).
11. Nahrendorf M, Swirski FK, Aikawa E et al. The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions. J. Exp. Med. 204(12), 3037-3047 (2007).
12. Yan ZQ, Hansson GK. Innate immunity, macrophage activation, and atherosclerosis. Immunol. Rev. 219, 187-203 (2007).
13. Weber C, Zernecke A, Libby P. The multifaceted contributions of leukocyte subsets to atherosclerosis: lessons from mouse models. Nat. Rev. Immunol. 8(10), 802-815 (2008).
14. Naghavi M, Libby P, Falk E et al. From vulnerable plaque to vulnerable patient: a call for new defnitions and risk assessment strategies: Part I. Circulation 108(14), 1664-1672 (2003). (Pubitemid 37243650)
15. Virmani R, Burke AP, Farb A, Kolodgie FD. Pathology of the vulnerable plaque. J. Am. Coll. Cardiol. 47(8 Suppl.), C13-C18 (2006).
16. Hansson G, Libby P, Schonbeck U, Yan Z. Innate and adaptive immunity in the pathogenesis of atherosclerosis. Circ. Res. 91(4), 281-291 (2002).
17. Full L, Ruisanchez C, Monaco C. The inextricable link between atherosclerosis and prototypical infammatory diseases rheumatoid arthritis and systemic lupus erythematosus. Arthritis Res. Ther. 11(2), 217 (2009).
18. Ross R. Atherosclerosis-an infammatory disease. N. Engl. J. Med. 340(2), 115-126 (1999).
19. O'Neill LA. The interleukin-1 receptor/Toll-like receptor superfamily: 10 years of progress. Immunol. Rev. 226, 10-18 (2008).
20. Hennessy EJ, Parker AE, O'Neill LA. Targeting Toll-like receptors: emerging therapeutics? Nat. Rev. Drug Discov. 9(4), 293-307 (2010).
21. Takeda K, Akira S. TLR signaling pathways. Semin. Immunol. 16(1), 3-9 (2004).
22. Liu L, Botos I, Wang Y et al. Structural basis of Toll-like receptor 3 signaling with double-stranded RNA. Science 320(5874), 379-381 (2008).
23. O'Neill L, Bowie A. The family of fve: TIR-domain-containing adaptors in Toll-like receptor signalling. Nat. Rev. Immunol. 7(5), 353-364 (2007).
24. Stewart CR, Stuart LM, Wilkinson K et al CD36 ligands promote sterile infammation through assembly of a Toll-like receptor 4 and 6 heterodimer. Nat. Immunol. 11(2), 155-161 (2010).
25. Hoebe K, Georgel P, Rutschmann S et al. CD36 is a sensor of diacylglycerides. Nature 433(7025), 523-527 (2005).
26. Takeuchi O, Akira S. Pattern recognition receptors and infammation. Cell 140(6), 805-820 (2010).
27. Takeuchi O, Takeda K, Hoshino K, Adachi O, Ogawa T, Akira S. Cellular responses to bacterial cell wall components are mediated through MyD88-dependent signaling cascades. Int. Immunol. 12(1), 113-117 (2000).
28. Hacker H, Vabulas RM, Takeuchi O, Hoshino K, Akira S, Wagner H. Immune cell activation by bacterial CpG-DNA through myeloid differentiation marker 88 and tumor necrosis factor receptor-associated factor (TRAF)6. J. Exp. Med. 192(4), 595-600 (2000).
29. Hemmi H, Kaisho T, Takeuchi O et al. Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway. Nat. Immunol. 3(2), 196-200 (2002).
30. Schnare M, Holt AC, Takeda K, Akira S, Medzhitov R. Recognition of CpG DNA is mediated by signaling pathways dependent on the adaptor protein MyD88. Curr. Biol. 10(18), 1139-1142 (2000).
31. Takeuchi O, Kaufmann A, Grote K et al. Cutting edge: preferentially the R-stereoisomer of the mycoplasmal lipopeptide macrophage-activating lipopeptide-2 activates immune cells through a Toll-like receptor 2-and MyD88-dependent signaling pathway. J. Immunol. 164(2), 554-557 (2000).
32. Sato M, Suemori H, Hata N et al. Distinct and essential roles of transcription factors IRF-3 and IRF-7 in response to viruses for IFN-a/b gene induction. Immunity 13(4), 539-548 (2000).
33. Weaver BK, Kumar KP, Reich NC. Interferon regulatory factor 3 and CREB-binding protein/p300 are subunits of double-stranded RNA-activated transcription factor DRAF1. Mol. Cell. Biol. 18(3), 1359-1368 (1998).
34. Yoneyama M, Suhara W, Fukuhara Y, Fukuda M, Nishida E, Fujita T. Direct triggering of the type I interferon system by virus infection: activation of a transcription factor complex containing IRF-3 and CBP/p300. EMBO J. 17(4), 1087-1095 (1998).
35. Blasius AL, Beutler B. Intracellular Toll-like receptors. Immunity 32(3), 305-315 (2010).
36. Carty M, Goodbody R, Schroder M, Stack J, Moynagh PN, Bowie AG. The human adaptor SARM negatively regulates adaptor protein TRIF-dependent Toll-like receptor signaling. Nat. Immunol. 7(10), 1074-1081 (2006).
37. Oganesyan G, Saha SK, Guo B et al. Critical role of TRAF3 in the Toll-like receptor-dependent and-independent antiviral response. Nature 439(7073), 208-211 (2006).
38. Alexopoulou L, Holt A, Medzhitov R, Flavell R. Recognition of double-stranded RNA and activation of NF-kB by Toll-like receptor 3. Nature 413(6857), 732-738 (2001).
39. Kawai T, Akira S. TLR signaling. Cell Death Differ. 13(5), 816-825 (2006).
40. Kawai T, Takeuchi O, Fujita T et al. Lipopolysaccharide stimulates the MyD88-independent pathway and results in activation of IFN-regulatory factor 3 and the expression of a subset of lipopolysaccharide-inducible genes. J. Immunol. 167(10), 5887-5894 (2001).
41. Doyle S, Vaidya S, O'Connell R et al. IRF3 mediates a TLR3/TLR4-specifc antiviral gene program. Immunity 17(3), 251-263 (2002).
42. Hoshino K, Kaisho T, Iwabe T, Takeuchi O, Akira S. Differential involvement of IFN-b in Toll-like receptor-stimulated dendritic cell activation. Int. Immunol. 14(10), 1225-1231 (2002).
43. Schroder NW, Morath S, Alexander C et al. Lipoteichoic acid (LTA) of Streptococcus pneumoniae and Staphylococcus aureus activates immune cells via Toll-like receptor (TLR)-2, lipopolysaccharide-binding protein (LBP), and CD14, whereas TLR-4 and MD-2 are not involved. J. Biol. Chem. 278(18), 15587-15594 (2003).
44. Underhill DM, Ozinsky A, Smith KD, Aderem A. Toll-like receptor-2 mediates mycobacteria-induced proinfammatory signaling in macrophages. Proc. Natl Acad. Sci. USA 96(25), 14459-14463 (1999).
45. Underhill DM, Ozinsky A, Hajjar AM et al. The Toll-like receptor 2 is recruited to macrophage phagosomes and discriminates between pathogens. Nature 401(6755), 811-815 (1999).
46. Brightbill HD, Libraty DH, Krutzik SR et al. Host defense mechanisms triggered by microbial lipoproteins through Toll-like receptors. Science 285(5428), 732-736 (1999).
47. Takeuchi O, Kawai T, Muhlradt P et al. Discrimination of bacterial lipoproteins by Toll-like receptor 6. Int. Immunol. 13(7), 933-940 (2001).
48. Gantner BN, Simmons RM, Canavera SJ, Akira S, Underhill DM. Collaborative induction of infammatory responses by dectin-1 and Toll-like receptor 2. J. Exp. Med. 197(9), 1107-1117 (2003).
49. Ozinsky A, Underhill DM, Fontenot JD et al. The repertoire for pattern recognition of pathogens by the innate immune system is defned by cooperation between Toll-like receptors. Proc. Natl Acad. Sci. USA 97(25), 13766-13771 (2000).
50. Brodsky I, Monack D. NLR-mediated control of infammasome assembly in the host response against bacterial pathogens. Semin. Immunol. 21(4), 199-207 (2009).
51. Jin MS, Kim SE, Heo JY et al. Crystal structure of the TLR1-TLR2 heterodimer induced by binding of a tri-acylated lipopeptide. Cell 130(6), 1071-1082 (2007).
52. Takeuchi O, Sato S, Horiuchi T et al. Cutting edge: role of Toll-like receptor 1 in mediating immune response to microbial lipoproteins. J. Immunol. 169(1), 10-14 (2002).
53. Hajishengallis G, Wang M, Bagby G, Nelson S. Importance of TLR2 in early innate immune response to acute pulmonary infection with Porphyromonas gingivalis in mice. J. Immunol. 181(6), 4141-4149 (2008).
54. Nakamura N, Yoshida M, Umeda M et al. Extended exposure of lipopolysaccharide fraction from Porphyromonas gingivalis facilitates mononuclear cell adhesion to vascular endothelium via Toll-like receptor-2 dependent mechanism. Atherosclerosis 196(1), 59-67 (2008).
55. Johnsen IB, Nguyen TT, Ringdal M et al. Toll-like receptor 3 associates with c-Src tyrosine kinase on endosomes to initiate antiviral signaling. EMBO J. 25(14), 3335-3346 (2006).
56. Lee HK, Dunzendorfer S, Soldau K, Tobias PS. Double-stranded RNA-mediated TLR3 activation is enhanced by CD14. Immunity 24(2), 153-163 (2006).
57. Shimazu R, Akashi S, Ogata H et al. MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4. J. Exp. Med. 189(11), 1777-1782 (1999).
58. Wright SD, Ramos RA, Tobias PS, Ulevitch RJ, Mathison JC. CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein. Science 249(4975), 1431-1433 (1990).
59. Chiu B, Viira E, Tucker W, Fong IW. Chlamydia pneumoniae, cytomegalovirus, and herpes simplex virus in atherosclerosis of the carotid artery. Circulation 96(7), 2144-2148 (1997).
60. Kuo C, Gown A, Benditt E, Grayston J. Detection of Chlamydia pneumoniae in aortic lesions of atherosclerosis by immunocytochemical stain. Arterioscler. Thromb. 13(10), 1501-1504 (1993).
61. Kuo C, Shor A, Campbell L, Fukushi H, Patton D, Grayston J. Demonstration of Chlamydia pneumoniae in atherosclerotic lesions of coronary arteries. J. Infect. Dis. 167(4), 841-849 (1993).
62. Burns E, Bachrach G, Shapira L, Nussbaum G. Cutting Edge: TLR2 is required for the innate response to Porphyromonas gingivalis: activation leads to bacterial persistence and TLR2 defciency attenuates induced alveolar bone resorption. J. Immunol. 177(12), 8296-8300 (2006).
63. Compton T, Kurt-Jones E, Boehme K et al. Human cytomegalovirus activates infammatory cytokine responses via CD14 and Toll-like receptor 2. J. Virol. 77(8), 4588-4596 (2003).
64. Naiki Y, Sorrentino R, Wong MH et al. TLR/MyD88 and liver X receptor a signaling pathways reciprocally control Chlamydia pneumoniae-induced acceleration of atherosclerosis. J. Immunol. 181(10), 7176-7185 (2008).
65. Kalayoglu M V, Libby P, Byrne GI. Chlamydia pneumoniae as an emerging risk factor in cardiovascular disease. JAMA 88(21), 2724-2731 (2002).
66. Kiechl S, Egger G, Mayr M et al. Chronic infections and the risk of carotid atherosclerosis: prospective results from a large population study. Circulation 103(8), 1064-1070 (2001).
67. Scannapieco FA, Bush RB, Paju S. Associations between periodontal disease and risk for atherosclerosis, cardiovascular disease, and stroke. A systematic review. Ann. Periodontol. 8(1), 38-53 (2003).
68. Wiedermann CJ, Kiechl S, Dunzendorfer S et al. Association of endotoxemia with carotid atherosclerosis and cardiovascular disease: prospective results from the Bruneck Study. J. Am. Coll. Cardiol. 34(7), 1975-1981 (1999).
69. Lehtiniemi J, Karhunen PJ, Goebeler S, Nikkari S, Nikkari ST. Identifcation of different bacterial DNAs in human coronary arteries. Eur. J. Clin. Invest. 35(1), 13-16 (2005).
70. Ott S, El Mokhtari N, Musfeldt M et al. Detection of diverse bacterial signatures in atherosclerotic lesions of patients with coronary heart disease. Circulation 113(7), 929-937 (2006).
71. Laman JD, Schoneveld AH, Moll FL, van Meurs M, Pasterkamp G. Signifcance of peptidoglycan, a proinfammatory bacterial antigen in atherosclerotic arteries and its association with vulnerable plaques. Am. J. Cardiol. 90(2), 119-123 (2002).
72. Park HK, Park EC, Bae SW et al. Expression of heat shock protein 27 in human atherosclerotic plaques and increased plasma level of heat shock protein 27 in patients with acute coronary syndrome. Circulation 114(9), 886-893 (2006).
73. Rifkin I, Leadbetter E, Busconi L, Viglianti G, Marshak-Rothstein A. Toll-like receptors, endogenous ligands, and systemic autoimmune disease. Immunol. Rev. 204, 27-42 (2005). (Pubitemid 40460491)
74. Lee J, Ye J, Gao Z et al. Reciprocal modulation of Toll-like receptor-4 signaling pathways involving MyD88 and phosphatidylinositol 3-kinase/AKT by saturated and polyunsaturated fatty acids. J. Biol. Chem. 278(39), 37041-37051 (2003).
75. Erridge C, Samani NJ. Saturated fatty acids do not directly stimulate Toll-like receptor signaling. Arterioscler. Thromb. Vasc. Biol. 29(11), 1944-1949 (2009).
76. Kawakami A, Osaka M, Aikawa M et al. Toll-like receptor 2 mediates apolipoprotein CIII-induced monocyte activation. Circ. Res. 103(12), 1402-1409 (2008).
77. Bae YS, Lee JH, Choi SH 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. 104(2), 210-218, 221p following 218 (2009).
78. Miller YI, Viriyakosol S, Binder CJ, Feramisco JR, Kirkland TN, Witztum JL. Minimally modifed LDL binds to CD14, induces macrophage spreading via TLR4/MD-2, and inhibits phagocytosis of apoptotic cells. J. Biol. Chem. 278(3), 1561-1568 (2003).
79. Midwood K, Sacre S, Piccinini AM et al. Tenascin-C is an endogenous activator of Toll-like receptor 4 that is essential for maintaining infammation in arthritic joint disease. Nat. Med. 15(7), 774-780 (2009).
80. Smiley ST, King JA, Hancock W W. Fibrinogen stimulates macrophage chemokine secretion through Toll-like receptor 4. J. Immunol. 167(5), 2887-2894 (2001).
81. Van Keulen JK, De Kleijn DP, Nijhuis MM et al. Levels of extra domain A containing fbronectin in human atherosclerotic plaques are associated with a stable plaque phenotype. Atherosclerosis 195(1), e83-e91 (2007).
82. Scheibner K, Lutz M, Boodoo S, Fenton M, Powell J, Horton M. Hyaluronan fragments act as an endogenous danger signal by engaging TLR2. J. Immunol. 177(2), 1272-1281 (2006).
83. Taylor K, Trowbridge J, Rudisill J, Termeer C, Simon J, Gallo R. Hyaluronan fragments stimulate endothelial recognition of injury through TLR4. J. Biol. Chem. 279(17), 17079-17084 (2004).
84. Termeer C, Benedix F, Sleeman J et al. Oligosaccharides of hyaluronan activate dendritic cells via Toll-like receptor 4. J. Exp. Med. 195(1), 99-111 (2002).
85. Schaefer L, Babelova A, Kiss E et al. The matrix component biglycan is proinfammatory and signals through Toll-like receptors 4 and 2 in macrophages. J. Clin. Invest. 115(8), 2223-2233 (2005).
86. Kim S, Takahashi H, Lin WW et al. Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis. Nature 457(7225), 102-106 (2009).
87. Kariko K, Ni H, Capodici J, Lamphier M, Weissman D. mRNA is an endogenous ligand for Toll-like receptor 3. J. Biol. Chem. 279(13), 12542-12550 (2004).
88. Asea A, Rehli M, Kabingu E et al. Novel signal transduction pathway utilized by extracellular HSP70: role of Toll-like receptor (TLR) 2 and TLR4. J. Biol. Chem. 277(17), 15028-15034 (2002).
89. Bulut Y, Faure E, Thomas L et al. Chlamydial heat shock protein 60 activates macrophages and endothelial cells through Toll-like receptor 4 and MD2 in a MyD88-dependent pathway. J. Immunol. 168(3), 1435-1440 (2002).
90. Da Costa C, Wantia N, Kirschning C et al. Heat shock protein 60 from Chlamydia pneumoniae elicits an unusual set of infammatory responses via Toll-like receptor 2 and 4 in vivo. Eur. J. Immunol. 34(10), 2874-2884 (2004).
91. De Graaf R, Kloppenburg G, Kitslaar P, Bruggeman C, Stassen F. Human heat shock protein 60 stimulates vascular smooth muscle cell proliferation through Toll-like receptors 2 and 4. Microbes Infect. 8(7), 1859-1865 (2006).
92. Kanwar RK, Kanwar JR, Wang D, Ormrod DJ, Krissansen GW. Temporal expression of heat shock proteins 60 and 70 at lesion-prone sites during atherogenesis in ApoE-defcient mice. Arterioscler. Thromb. Vasc. Biol. 21(12), 1991-1997 (2001).
93. Ohashi K, Burkart V, Flohe S, Kolb H. Cutting edge: heat shock protein 60 is a putative endogenous ligand of the Toll-like receptor-4 complex. J. Immunol. 164(2), 558-561 (2000).
94. Vabulas R, Ahmad-Nejad P, Ghose S, Kirschning C, Issels R, Wagner H. HSP70 as endogenous stimulus of the Toll/interleukin-1 receptor signal pathway. J. Biol. Chem. 277(17), 15107-15112 (2002).
95. Vabulas R, Braedel S, Hilf N et al. The endoplasmic reticulum-resident heat shock protein Gp96 activates dendritic cells via the Toll-like receptor 2/4 pathway. J. Biol. Chem. 277(23), 20847-20853 (2002).
96. Zanin-Zhorov A, Nussbaum G, Franitza S, Cohen IR, Lider O. T cells respond to heat shock protein 60 via TLR2: activation of adhesion and inhibition of chemokine receptors. FASEB J. 17(11), 1567-1569 (2003).
97. Porto A, Palumbo R, Pieroni M et al. Smooth muscle cells in human atherosclerotic plaques secrete and proliferate in response to high mobility group box 1 protein. FASEB J. 20(14), 2565-2566 (2006).
98. Park J, Svetkauskaite D, He Q et al. Involvement of Toll-like receptors 2 and 4 in cellular activation by high mobility group box 1 protein. J. Biol. Chem. 279(9), 7370-7377 (2004).
99. Bsibsi M, Bajramovic JJ, Vogt MH et al. The microtubule regulator stathmin is an endogenous protein agonist for TLR3. J. Immunol. 184(12), 6929-6937 (2010).
100. Erridge C, Burdess A, Jackson AJ et al. Vascular cell responsiveness to Toll-like receptor ligands in carotid atheroma. Eur. J. Clin. Invest. 38(10), 713-720 (2008).
101. Pryshchep O, Ma-Krupa W, Younge B, Goronzy J, Weyand C. Vessel-specifc Toll-like receptor profles in human medium and large arteries. Circulation 118(12), 1276-1284 (2008).
102. Edfeldt K, Swedenborg J, Hansson G, Yan Z. Expression of Toll-like receptors in human atherosclerotic lesions: a possible pathway for plaque activation. Circulation 105(10), 1158-1161 (2002).
103. Cole JE, Georgiou E, Monaco C. The expression and functions of Toll-like receptors in atherosclerosis. Mediators Infamm. 393946 (2010).
104. Kadowaki N, Ho S, Antonenko S et al. Subsets of human dendritic cell precursors express different Toll-like receptors and respond to different microbial antigens. J. Exp. Med. 194(6), 863-869 (2001).
105. Visintin A, Mazzoni A, Spitzer J, Wyllie D, Dower S, Segal D. Regulation of Toll-like receptors in human monocytes and dendritic cells. J. Immunol. 166(1), 249-255 (2001).
106. Geng H, Lu H, Zhang L et al. Increased expression of Toll like receptor 4 on peripheral-blood mononuclear cells in patients with coronary arteriosclerosis disease. Clin. Exp. Immunol. 143(2), 269-273 (2006).
107. Methe H, Kim J, Kofer S, Weis M, Nabauer M, Koglin J. Expansion of circulating Toll-like receptor 4-positive monocytes in patients with acute coronary syndrome. Circulation 111(20), 2654-2661 (2005).
108. Shiraki R, Inoue N, Kobayashi S et al. Toll-like receptor 4 expressions on peripheral blood monocytes were enhanced in coronary artery disease even in patients with low C-reactive protein. Life Sci. 80(1), 59-66 (2006).
109. Kuwahata S, Fujita S, Orihara K et al. High expression level of Toll-like receptor 2 on monocytes is an important risk factor for arteriosclerotic disease. Atherosclerosis 209(1), 248-254 (2010).
110. Ashida K, Miyazaki K, Takayama E et al. Characterization of the expression of TLR2 (Toll-like receptor 2) and TLR4 on circulating monocytes in coronary artery disease. J. Atheroscler. Thromb. 12(1), 53-60 (2005).
111. Liuzzo G, Angiolillo DJ, Buffon A et al. Enhanced response of blood monocytes to in vitro lipopolysaccharide-challenge in patients with recurrent unstable angina. Circulation 103(18), 2236-2241 (2001).
112. Versteeg D, Hoefer IE, Schoneveld AH et al. Monocyte Toll-like receptor 2 and 4 responses and expression following percutaneous coronary intervention: association with lesion stenosis and fractional fow reserve. Heart 94(6), 770-776 (2008).
113. Schoneveld A, Hoefer I, Sluijter J, Laman J, de Kleijn D, Pasterkamp G. Atherosclerotic lesion development and Toll like receptor 2 and 4 responsiveness. Atherosclerosis 197(1), 95-104 (2008).
114. Moreno-Altamirano MM, Aguilar-Carmona I, Sanchez-Garcia FJ. Expression of GM1, a marker of lipid rafts, defnes two subsets of human monocytes with differential endocytic capacity and lipopolysaccharide responsiveness. Immunology 120(4), 536-543 (2007).
115. Swirski FK, Weissleder R, Pittet MJ. Heterogeneous in vivo behavior of monocyte subsets in atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 29(10), 1424-1432 (2009).
116. Barbalat R, Lau L, Locksley R, Barton G. Toll-like receptor 2 on infammatory monocytes induces type I interferon in response to viral but not bacterial ligands. Nat. Immunol. 10(11), 1200-1207 (2009).
117. Holvoet P, Davey PC, De Keyzer D et al. Oxidized low-density lipoprotein correlates positively with Toll-like receptor 2 and interferon regulatory factor-1 and inversely with superoxide dismutase-1 expression: studies in hypercholesterolemic swine and THP-1 cells. Arterioscler. Thromb. Vasc. Biol. 26(7), 1558-1565 (2006).
118. Xu XH, Shah PK, Faure E et al. Toll-like receptor-4 is expressed by macrophages in murine and human lipid-rich atherosclerotic plaques and upregulated by oxidized LDL. Circulation 104(25), 3103-3108 (2001).
119. Ahn KO, Lim SW, Li C et al. Infuence of angiotensin II on expression of Toll-like receptor 2 and maturation of dendritic cells in chronic cyclosporine nephropathy. Transplantation 83(7), 938-947 (2007).
120. Dasu MR, Riosvelasco AC, Jialal I. Candesartan inhibits Toll-like receptor expression and activity both in vitro and in vivo. Atherosclerosis 202(1), 76-83 (2009).
121. Foldes G, von Haehling S, Okonko DO, Jankowska EA, Poole-Wilson PA, Anker SD. Fluvastatin reduces increased blood monocyte Toll-like receptor 4 expression in whole blood from patients with chronic heart failure. Int. J. Cardiol. 124(1), 80-85 (2008).
122. Ghanim H, Mohanty P, Deopurkar R et al. Acute modulation of Toll-like receptors by insulin. Diabetes Care 31(9), 1827-1831 (2008).
123. Niessner A, Sato K, Chaikof E, Colmegna I, Goronzy J, Weyand C. Pathogen-sensing plasmacytoid dendritic cells stimulate cytotoxic T-cell function in the atherosclerotic plaque through interferon-a. Circulation 114(23), 2482-2489 (2006).
124. Bobryshev Y V, Lord RS. Ultrastructural recognition of cells with dendritic cell morphology in human aortic intima. Contacting interactions of vascular dendritic cells in athero-resistant and athero-prone areas of the normal aorta. Arch. Histol. Cytol. 58(3), 307-322 (1995).
125. Jongstra-Bilen J, Haidari M, Zhu S, Chen M, Guha D, Cybulsky M. Low-grade chronic infammation in regions of the normal mouse arterial intima predisposed to atherosclerosis. J. Exp. Med. 203(9), 2073-2083 (2006).
126. Millonig G, Malcom G, Wick G. Early infammatory-immunological lesions in juvenile atherosclerosis from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY)-study. Atherosclerosis 160(2), 441-448 (2002).
127. Millonig G, Niederegger H, Rabl W et al. Network of vascular-associated dendritic cells in intima of healthy young individuals. Arterioscler. Thromb. Vasc. Biol. 21(4), 503-508 (2001).
128. Lord RS, Bobryshev Y V. Clustering of dendritic cells in athero-prone areas of the aorta. Atherosclerosis 146(1), 197-198 (1999).
129. Erbel C, Sato K, Meyer F et al. Functional profle of activated dendritic cells in unstable atherosclerotic plaque. Basic Res. Cardiol. 102(2), 123-132 (2007).
130. Jarrossay D, Napolitani G, Colonna M, Sallusto F, Lanzavecchia A. Specialization and complementarity in microbial molecule recognition by human myeloid and plasmacytoid dendritic cells. Eur. J. Immunol. 31(11), 3388-3393 (2001).
131. Krug A, Towarowski A, Britsch S et al. Toll-like receptor expression reveals CpG DNA as a unique microbial stimulus for plasmacytoid dendritic cells which synergizes with CD40 ligand to induce high amounts of IL-12. Eur. J. Immunol. 31(10), 3026-3037 (2001). (Pubitemid 32994554)
132. Matsumoto M, Funami K, Tanabe M et al. Subcellular localization of Toll-like receptor 3 in human dendritic cells. J. Immunol. 171(6), 3154-3162 (2003).
133. Ito T, Amakawa R, Kaisho T et al. Interferon-a and interleukin-12 are induced differentially by Toll-like receptor 7 ligands in human blood dendritic cell subsets. J. Exp. Med. 195(11), 1507-1512 (2002).
134. Kaartinen M, Penttila A, Kovanen P. Mast cells of two types differing in neutral protease composition in the human aortic intima. Demonstration of tryptase-and tryptase/chymase-containing mast cells in normal intimas, fatty streaks, and the shoulder region of atheromas. Arterioscler. Thromb. 14(6), 966-972 (1994).
135. Kulka M, Alexopoulou L, Flavell RA, Metcalfe DD. Activation of mast cells by double-stranded RNA: evidence for activation through Toll-like receptor 3. J. Allergy Clin. Immunol. 114(1), 174-182 (2004).
136. Marshall JS. Mast-cell responses to pathogens. Nat. Rev. Immunol. 4(10), 787-799 (2004).
137. McCurdy JD, Olynych TJ, Maher LH, Marshall JS. Cutting edge: distinct Toll-like receptor 2 activators selectively induce different classes of mediator production from human mast cells. J. Immunol. 170(4), 1625-1629 (2003).
138. Okumura S, Kashiwakura J, Tomita H et al. Identifcation of specifc gene expression profles in human mast cells mediated by Toll-like receptor 4 and FceRI. Blood 102(7), 2547-2554 (2003).
139. Supajatura V, Ushio H, Nakao A, Okumura K, Ra C, Ogawa H. Protective roles of mast cells against enterobacterial infection are mediated by Toll-like receptor 4. J. Immunol. 167(4), 2250-2256 (2001).
140. Bot I, de Jager SC, Bot M et al. The neuropeptide substance P mediates adventitial mast cell activation and induces intraplaque hemorrhage in advanced atherosclerosis. Circ. Res. 106(1), 89-92 (2009).
141. Tancowny BP, Karpov V, Schleimer RP, Kulka M. Substance P primes lipoteichoic acid-and Pam3CysSerLys4-mediated activation of human mast cells by up-regulating Toll-like receptor 2. Immunology 131(2), 220-230 (2010).
142. Mullick AE, Soldau K, Kiosses WB, Bell TA 3rd, Tobias PS, Curtiss LK. Increased endothelial expression of Toll-like receptor 2 at sites of disturbed blood fow exacerbates early atherogenic events. J. Exp. Med. 205(2), 373-383 (2008).
143. Dunzendorfer S, Lee HK, Tobias PS. Flow-dependent regulation of endothelial Toll-like receptor 2 expression through inhibition of SP1 activity. Circ. Res. 95(7), 684-691 (2004).
144. Chaudhury H, Zakkar M, Boyle J et al. c-Jun N-terminal kinase primes endothelial cells at atheroprone sites for apoptosis. Arterioscler. Thromb. Vasc. Biol. 30(3), 546-553 (2010).
145. Yang X, Murthy V, Schultz K, Tatro J, Fitzgerald K, Beasley D. Toll-like receptor 3 signaling evokes a proinfammatory and proliferative phenotype in human vascular smooth muscle cells. Am. J. Physiol. Heart Circ. Physiol. 291(5), H2334-2343 (2006).
146. Yang X, Coriolan D, Schultz K, Golenbock DT, Beasley D. Toll-like receptor 2 mediates persistent chemokine release by Chlamydia pneumoniae-infected vascular smooth muscle cells. Arterioscler. Thromb. Vasc. Biol. 25(11), 2308-2314 (2005).
147. Hong TJ, Ban JE, Choi KH et al. TLR-4 agonistic lipopolysaccharide upregulates interleukin-8 at the transcriptional and post-translational level in vascular smooth muscle cells. Vascul. Pharmacol. 50(1-2), 34-39 (2009).
148. Stoll LL, Denning GM, Weintraub NL. Potential role of endotoxin as a proinfammatory mediator of atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 24(12), 2227-2236 (2004).
149. Galkina E, Kadl A, Sanders J, Varughese D, Sarembock I, Ley K. Lymphocyte recruitment into the aortic wall before and during development of atherosclerosis is partially L-selectin dependent. J. Exp. Med. 203(5), 1273-1282 (2006).
150. -/- mice. J. Exp. Med. 206(1), 233-248 (2009).
151. Houtkamp M, de Boer O, van der Loos C, van der Wal A, Becker A. Adventitial infltrates associated with advanced atherosclerotic plaques: structural organization suggests generation of local humoral immune responses. J. Pathol. 193(2), 263-269 (2001).
152. Vink A, Schoneveld AH, van der Meer JJ et al. In vivo evidence for a role of Toll-like receptor 4 in the development of intimal lesions. Circulation 106(15), 1985-1990 (2002).
153. Schoneveld AH, Oude Nijhuis MM, van Middelaar B, Laman JD, de Kleijn DP, Pasterkamp G. Toll-like receptor 2 stimulation induces intimal hyperplasia and atherosclerotic lesion development. Cardiovasc. Res. 66(1), 162-169 (2005).
154. + DC correlates with unresponsiveness to imidazoquinolines. Eur. J. Immunol. 33(4), 827-833 (2003).
155. Chen S, Wong MH, Schulte DJ, Arditi M, Michelsen KS. Differential expression of Toll-like receptor 2 (TLR2) and responses to TLR2 ligands between human and murine vascular endothelial cells. J. Endotoxin Res. 13(5), 281-296 (2007).
156. Funk JL, Feingold KR, Moser AH, Grunfeld C. Lipopolysaccharide stimulation of R AW 264.7 macrophages induces lipid accumulation and foam cell formation. Atherosclerosis 98(1), 67-82 (1993).
157. Kim JS, Park DW, Lee HK, Kim JR, Baek SH. Early growth response-1 is involved in foam cell formation and is upregulated by the TLR9-MyD88-ERK1/2 pathway. Biochem. Biophys. Res. Commun. 390(2), 196-200 (2009).
158. Lee J, Lim E, Park D, Lee S, Kim J, Baek S. A combination of Lox-1 and Nox1 regulates TLR9-mediated foam cell formation. Cell Signal. 20(12), 2266-2275 (2008).
159. Oiknine J, Aviram M. Increased susceptibility to activation and increased uptake of low density lipoprotein by cholesterol-loaded macrophages. Arterioscler. Thromb. 12(6), 745-753 (1992).
160. Cao F, Castrillo A, Tontonoz P, Re F, Byrne GI. Chlamydia pneumoniae-induced macrophage foam cell formation is mediated by Toll-like receptor 2. Infect. Immun. 75(2), 753-759 (2007).
161. Chen S, Sorrentino R, Shimada K et al. Chlamydia pneumoniae-induced foam cell formation requires MyD88-dependent and-independent signaling and is reciprocally modulated by liver X receptor activation. J. Immunol. 181(10), 7186-7193 (2008).
162. Choi S, Harkewicz R, Lee J et al. Lipoprotein accumulation in macrophages via Toll-like receptor-4-dependent fuid phase uptake. Circ. Res. 104(12), 1355-1363 (2009).
163. Doyle S, O'Connell R, Miranda G et al. Toll-like receptors induce a phagocytic gene program through p38. J. Exp. Med. 199(1), 81-90 (2004).
164. Feingold KR, Kazemi MR, Magra AL et al. ADRP/ADFP and Mal1 expression are increased in macrophages treated with TLR agonists. Atherosclerosis 209(1), 81-88 (2010).
165. Kazemi M, McDonald C, Shigenaga J, Grunfeld C, Feingold K. Adipocyte fatty acid-binding protein expression and lipid accumulation are increased during activation of murine macrophages by Toll-like receptor agonists. Arterioscler. Thromb. Vasc. Biol. 25(6), 1220-1224 (2005).
166. Castrillo A, Joseph S, Vaidya S et al. Crosstalk between LXR and Toll-like receptor signaling mediates bacterial and viral antagonism of cholesterol metabolism. Mol. Cell 12(4), 805-816 (2003).
167. Poltorak A, He X, Smirnova I et al. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in TLR4 gene. Science 282(5396), 2085-2088 (1998).
168. Qureshi ST, Lariviere L, Leveque G et al. Endotoxin-tolerant mice have mutations in Toll-like receptor 4 (TLR4). J. Exp. Med. 189(4), 615-625 (1999).
169. Ishida B, Blanche P, Nichols A, Yashar M, Paigen B. Effects of atherogenic diet consumption on lipoproteins in mouse strains C57BL/6 and C3H. J. Lipid Res. 32(4), 559-568 (1991).
170. Nishina P, Wang J, Toyofuku W, Kuypers F, Ishida B, Paigen B. Atherosclerosis and plasma and liver lipids in nine inbred strains of mice. Lipids 28(7), 599-605 (1993).
171. Shi W, Wang NJ, Shih DM, Sun VZ, Wang X, Lusis AJ. Determinants of atherosclerosis susceptibility in the C3H and C57BL/6 mouse model: evidence for involvement of endothelial cells but not blood cells or cholesterol metabolism. Circ. Res. 86(10), 1078-1084 (2000).
172. Mullick A, Tobias P, Curtiss L. Modulation of atherosclerosis in mice by Toll-like receptor 2. J. Clin. Invest. 115(11), 3149-3156 (2005).
173. Michelsen KS, Wong MH, Shah PK et al. Lack of Toll-like receptor 4 or myeloid differentiation factor 88 reduces atherosclerosis and alters plaque phenotype in mice defcient in apolipoprotein E. Proc. Natl Acad. Sci. USA 101(29), 10679-10684 (2004).
174. Rekhter M, Staschke K, Estridge T et al. Genetic ablation of IRAK4 kinase activity inhibits vascular lesion formation. Biochem. Biophys. Res. Commun. 367(3), 642-648 (2008).
175. Kirii H, Niwa T, Yamada Y et al. Lack of interleukin-1p decreases the severity of atherosclerosis in ApoE-defcient mice. Arterioscler. Thromb. Vasc. Biol. 23(4), 656-660 (2003).
176. Merhi-Soussi F, Kwak BR, Magne D et al. Interleukin-1 plays a major role in vascular infammation and atherosclerosis in male apolipoprotein E-knockout mice. Cardiovasc. Res. 66(3), 583-593 (2005).
177. Isoda K, Sawada S, Ishigami N et al. Lack of interleukin-1 receptor antagonist modulates plaque composition in apolipoprotein E-defcient mice. Arterioscler. Thromb. Vasc. Biol. 24(6), 1068-1073 (2004).
178. Elhage R, Jawien J, Rudling M et al. Reduced atherosclerosis in interleukin-18 defcient apolipoprotein E-knockout mice. Cardiovasc. Res. 59(1), 234-240 (2003).
179. Liu X, Ukai T, Yumoto H et al. Toll-like receptor 2 plays a critical role in the progression of atherosclerosis that is independent of dietary lipids. Atherosclerosis 196(1), 146-154 (2008).
180. Coenen KR, Gruen ML, Lee-Young RS, Puglisi MJ, Wasserman DH, Hasty AH. Impact of macrophage Toll-like receptor 4 defciency on macrophage infltration into adipose tissue and the artery wall in mice. Diabetologia 52(2), 318-328 (2009).
181. Combadiere C, Potteaux S, Rodero M et al. Combined inhibition of CCL2, CX3CR1, and CCR5 abrogates Ly6C(hi) and Ly6C(lo) monocytosis and almost abolishes atherosclerosis in hypercholesterolemic mice. Circulation 117(13), 1649-1657 (2008).
182. Bjorkbacka H, Kunjathoor V V, Moore KJ et al. Reduced atherosclerosis in MyD88-null mice links elevated serum cholesterol levels to activation of innate immunity signaling pathways. Nat. Med. 10(4), 416-421 (2004).
183. Arbour NC, Lorenz E, Schutte BC et al. TLR4 mutations are associated with endotoxin hyporesponsiveness in humans. Nat. Genet. 25(2), 187-191 (2000).
184. Cook DN, Pisetsky DS, Schwartz DA. Toll-like receptors in the pathogenesis of human disease. Nat. Immunol. 5(10), 975-979 (2004).
185. Frantz S, Ertl G, Bauersachs J. Mechanisms of disease: Toll-like receptors in cardiovascular disease. Nat. Clin. Pract. Cardiovasc. Med. 4(8), 444-454 (2007).
186. Kiechl S, Lorenz E, Reindl M et al. Toll-like receptor 4 polymorphisms and atherogenesis. N. Engl. J. Med. 347(3), 185-192 (2002).
187. Labrum R, Bevan S, Sitzer M, Lorenz M, Markus HS. Toll receptor polymorphisms and carotid artery intima-media thickness. Stroke 38(4), 1179-1184 (2007). (Pubitemid 351664263)
188. Koch W, Hoppmann P, Pfeufer A, Schomig A, Kastrati A. Toll-like receptor 4 gene polymorphisms and myocardial infarction: no association in a Caucasian population. Eur. Heart J. 27(21), 2524-2529 (2006).
189. Hamann L, Gomma A, Schroder NW et al. A frequent Toll-like receptor (TLR)-2 polymorphism is a risk factor for coronary restenosis. J. Mol. Med. 83(6), 478-485 (2005).
190. O'Neill LA. Targeting signal transduction as a strategy to treat infammatory diseases. Nat. Rev. Drug Discov. 5(7), 549-563 (2006).
191. Mullarkey M, Rose JR, Bristol J et al. Inhibition of endotoxin response by e5564, a novel Toll-like receptor 4-directed endotoxin antagonist. J. Pharmacol. Exp. Ther. 304(3), 1093-1102 (2003).
192. Savov JD, Brass DM, Lawson BL, McElvania-Tekippe E, Walker JK, Schwartz DA. Toll-like receptor 4 antagonist (E5564) prevents the chronic airway response to inhaled lipopolysaccharide. Am. J. Physiol. Lung Cell. Mol. Physiol. 289(2), L329-L337 (2005).
193. Bennett-Guerrero E, Grocott HP, Levy JH et al. A Phase II, double-blind, placebo-controlled, ascending-dose study of Eritoran (E5564), a lipid A antagonist, in patients undergoing cardiac surgery with cardiopulmonary bypass. Anesth. Analg. 104(2), 378-383 (2007).
194. O'Neill LA. Therapeutic targeting of Toll-like receptors for infammatory and infectious diseases. Curr. Opin. Pharmacol. 3(4), 396-403 (2003).
195. Monaco C, Gregan SM, Navin TJ, Foxwell BM, Davies AH, Feldmann M. Toll-like receptor-2 mediates infammation and matrix degradation in human atherosclerosis. Circulation 120(24), 2462-2469 (2009).
196. Arslan F, Smeets M, O'Neill L et al. Myocardial ischemia/reperfusion injury is mediated by leukocytic Toll-like receptor-2 and reduced by systemic administration of a novel anti-Toll-like receptor-2 antibody Circulation 121(1), 80-90 (2010).
197. Bartfai T, Behrens MM, Gaidarova S, Pemberton J, Shivanyuk A, Rebek J Jr. A low molecular weight mimic of the Toll/IL-1 receptor/resistance domain inhibits IL-1 receptor-mediated responses. Proc. Natl Acad. Sci. USA 100(13), 7971-7976 (2003).
198. Brand K, Page S, Rogler G et al. Activated transcription factor nuclear factor-kB is present in the atherosclerotic lesion. J. Clin. Invest. 97(7), 1715-1722 (1996).
199. Monaco C, Paleolog E. Nuclear factor kB: a potential therapeutic target in atherosclerosis and thrombosis. Cardiovasc. Res. 61(4), 671-682 (2004).
200. Monaco C, Andreakos E, Kiriakidis S et al. Canonical pathway of nuclear factor kB activation selectively regulates proinfammatory and prothrombotic responses in human atherosclerosis. Proc. Natl Acad. Sci. USA 101(15), 5634-5639 (2004).
201. Dichtl W, Dulak J, Frick M et al. HMG-CoA reductase inhibitors regulate infammatory transcription factors in human endothelial and vascular smooth muscle cells. Arterioscler. Thromb. Vasc. Biol. 23(1), 58-63 (2003).
202. Ortego M, Bustos C, Hernandez-Presa MA et al. Atorvastatin reduces NF-kB activation and chemokine expression in vascular smooth muscle cells and mononuclear cells. Atherosclerosis 147(2), 253-261 (1999).
203. Gareus R, Kotsaki E, Xanthoulea S et al. Endothelial cell-specifc NF-kB inhibition protects mice from atherosclerosis. Cell Metab. 8(5), 372-383 (2008).
204. Kanters E, Pasparakis M, Gijbels MJ et al. Inhibition of NF-kB activation in macrophages increases atherosclerosis in LDL receptor-defcient mice. J. Clin. Invest. 112(8), 1176-1185 (2003).
205. Kanters E, Gijbels MJ, van der Made I et al. Hematopoietic NF-kB1 defciency results in small atherosclerotic lesions with an infammatory phenotype. Blood 103(3), 934-940 (2004).
206. English JM, Cobb MH. Pharmacological inhibitors of MAPK pathways. Trends Pharmacol. Sci. 23(1), 40-45 (2002).
207. Sheedy FJ, O'Neill LA. Adding fuel to fre: microRNAs as a new class of mediators of infammation. Ann. Rheum. Dis. 67(Suppl. 3), iii50-iii55 (2008).
208. O'Connell RM, Chaudhuri AA, Rao DS, Baltimore D. Inositol phosphatase SHIP1 is a primary target of miR-155. Proc. Natl Acad. Sci. USA 106(17), 7113-7118 (2009).
209. Tili E, Michaille JJ, Cimino A et al. Modulation of miR-155 and miR-125b levels following lipopolysaccharide/TNF-a stimulation and their possible roles in regulating the response to endotoxin shock. J. Immunol. 179(8), 5082-5089 (2007).
210. Fichtlscherer S, De Rosa S, Fox H et al. Circulating microRNAs in patients with coronary artery disease. Circ. Res. 107(5), 677-684 (2010).
211. Najaf-Shoushtari SH, Kristo F, Li Y et al. MicroRNA-33 and the SREBP host genes cooperate to control cholesterol homeostasis. Science 328(5985), 1566-1569 (2010).
212. Rayner KJ, Suarez Y, Davalos A et al. MiR-33 contributes to the regulation of cholesterol homeostasis. Science 328(5985), 1570-1573 (2010).
213. Bowie A, Kiss-Toth E, Symons JA, Smith GL, Dower SK, O'Neill LA. A46R and A52R from vaccinia virus are antagonists of host IL-1 and Toll-like receptor signaling. Proc. Natl Acad. Sci. USA 97(18), 10162-10167 (2000).
214. Harte MT, Haga IR, Maloney G et al. The poxvirus protein A52R targets Toll-like receptor signaling complexes to suppress host defense. J. Exp. Med. 197(3), 343-351 (2003).