(Circulation. 2002;105:1158.)
© 2002 American Heart Association, Inc.
Brief Rapid Communications |
From the Center for Molecular Medicine and the Department of Medicine (K.E., G.K.H., Z.-q.Y.) and the Department of Surgery (J.S.), Karolinska Institute, Stockholm, Sweden.
Correspondence to Dr Zhong-qun Yan, CMM L8:03, Karolinska Hospital, SE-17176 Stockholm, Sweden. E-mail Zhong-qun.Yan{at}cmm.ki.se
Background Innate immune reactions against bacteria and viruses have been implicated in the pathogenesis of atherosclerosis. To explore the molecular mechanism by which microbe recognition occurs in the artery wall, we characterized the expression of toll-like receptors (TLRs), a family of pathogen pattern recognition receptors, in atherosclerotic lesions.
Methods and Results Semiquantitative polymerase chain reaction and immunohistochemical analysis demonstrated that of 9 TLRs, the expression of TLR1, TLR2, and TLR4 was markedly enhanced in human atherosclerotic plaques. A considerable proportion of TLR-expressing cells were also activated, as shown by the nuclear translocation of nuclear factor-
B.
Conclusion Our findings illustrate a repertoire of TLRs associated with inflammatory activation in human atherosclerotic lesions, and they encourage further exploration of innate immunity in the pathogenesis of atherosclerosis.
Key Words: receptors atherosclerosis nuclear factor-
B immune system
This article has been cited by other articles:
![]() |
O. Pryshchep, W. Ma-Krupa, B. R. Younge, J. J. Goronzy, and C. M. Weyand Vessel-Specific Toll-Like Receptor Profiles in Human Medium and Large Arteries Circulation, September 16, 2008; 118(12): 1276 - 1284. [Abstract] [Full Text] [PDF] |
||||
![]() |
D Versteeg, I E Hoefer, A H Schoneveld, D P V de Kleijn, E Busser, C Strijder, M Emons, P R Stella, P A Doevendans, and G Pasterkamp Monocyte toll-like receptor 2 and 4 responses and expression following percutaneous coronary intervention: association with lesion stenosis and fractional flow reserve Heart, June 1, 2008; 94(6): 770 - 776. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Foglieni, F. Maisano, L. Dreas, A. Giazzon, G. Ruotolo, E. Ferrero, L. Li Volsi, S. Coli, G. Sinagra, B. Zingone, et al. Mild inflammatory activation of mammary arteries in patients with acute coronary syndromes Am J Physiol Heart Circ Physiol, June 1, 2008; 294(6): H2831 - H2837. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. I. Duenas, M. Aceves, I. Fernandez-Pisonero, C. Gomez, A. Orduna, M. S. Crespo, and C. Garcia-Rodriguez Selective attenuation of Toll-like receptor 2 signalling may explain the atheroprotective effect of sphingosine 1-phosphate Cardiovasc Res, May 12, 2008; (2008) cvn087v2. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Malarstig, S. Sigurdsson, P. Eriksson, G. Paulsson-Berne, U. Hedin, L. Wallentin, A. Siegbahn, A. Hamsten, and A.-C. Syvanen Variants of the Interferon Regulatory Factor 5 Gene Regulate Expression of IRF5 mRNA in Atherosclerotic Tissue But Are Not Associated With Myocardial Infarction Arterioscler. Thromb. Vasc. Biol., May 1, 2008; 28(5): 975 - 982. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Loppnow, K. Werdan, and M. Buerke Invited review: Vascular cells contribute to atherosclerosis by cytokine- and innate-immunity-related inflammatory mechanisms Innate Immunity, April 1, 2008; 14(2): 63 - 87. [Abstract] [PDF] |
||||
![]() |
A. E. Mullick, K. Soldau, W. B. Kiosses, T. A. Bell III, P. S. Tobias, and L. K. Curtiss Increased endothelial expression of Toll-like receptor 2 at sites of disturbed blood flow exacerbates early atherogenic events J. Exp. Med., February 18, 2008; 205(2): 373 - 383. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Fitzner, S. Clauberg, F. Essmann, J. Liebmann, and V. Kolb-Bachofen Human Skin Endothelial Cells Can Express All 10 TLR Genes and Respond to Respective Ligands Clin. Vaccine Immunol., January 1, 2008; 15(1): 138 - 146. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Westerterp, J. F.P. Berbee, N. M.M. Pires, G. J.D. van Mierlo, R. Kleemann, J. A. Romijn, L. M. Havekes, and P. C.N. Rensen Apolipoprotein C-I Is Crucially Involved in Lipopolysaccharide-Induced Atherosclerosis Development in Apolipoprotein E Knockout Mice Circulation, November 6, 2007; 116(19): 2173 - 2181. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Shinohara, K.-i. Hirata, T. Yamashita, T. Takaya, N. Sasaki, R. Shiraki, T. Ueyama, N. Emoto, N. Inoue, M. Yokoyama, et al. Local Overexpression of Toll-Like Receptors at the Vessel Wall Induces Atherosclerotic Lesion Formation: Synergism of TLR2 and TLR4 Arterioscler. Thromb. Vasc. Biol., November 1, 2007; 27(11): 2384 - 2391. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Niessner, M. S. Shin, O. Pryshchep, J. J. Goronzy, E. L. Chaikof, and C. M. Weyand Synergistic Proinflammatory Effects of the Antiviral Cytokine Interferon-{alpha} and Toll-Like Receptor 4 Ligands in the Atherosclerotic Plaque Circulation, October 30, 2007; 116(18): 2043 - 2052. [Abstract] [Full Text] [PDF] |
||||
![]() |
Shuang Chen, M. H. Wong, D. J. Schulte, M. Arditi, and K. S. Michelsen Differential expression of Toll-like receptor 2 (TLR2) and responses to TLR2 ligands between human and murine vascular endothelial cells Innate Immunity, October 1, 2007; 13(5): 281 - 296. [Abstract] [PDF] |
||||
![]() |
Y.-C. Chen, E. Giovannucci, P. Kraft, R. Lazarus, and D. J. Hunter Association between Toll-Like Receptor Gene Cluster (TLR6, TLR1, and TLR10) and Prostate Cancer Cancer Epidemiol. Biomarkers Prev., October 1, 2007; 16(10): 1982 - 1989. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. M. Lepper, C. Schumann, K. Triantafilou, F. M. Rasche, T. Schuster, H. Frank, E. M. Schneider, M. Triantafilou, and M. von Eynatten Association of Lipopolysaccharide-Binding Protein and Coronary Artery Disease in Men J. Am. Coll. Cardiol., July 3, 2007; 50(1): 25 - 31. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. K. Shah Innate Immune Pathway Links Obesity to Insulin Resistance Circ. Res., June 8, 2007; 100(11): 1531 - 1533. [Full Text] [PDF] |
||||
![]() |
F. Kim, M. Pham, I. Luttrell, D. D. Bannerman, J. Tupper, J. Thaler, T. R. Hawn, E. W. Raines, and M. W. Schwartz Toll-Like Receptor-4 Mediates Vascular Inflammation and Insulin Resistance in Diet-Induced Obesity Circ. Res., June 8, 2007; 100(11): 1589 - 1596. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Danese, E. Dejana, and C. Fiocchi Immune Regulation by Microvascular Endothelial Cells: Directing Innate and Adaptive Immunity, Coagulation, and Inflammation J. Immunol., May 15, 2007; 178(10): 6017 - 6022. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Labrum, S. Bevan, M. Sitzer, M. Lorenz, and H. S. Markus Toll Receptor Polymorphisms and Carotid Artery Intima-Media Thickness Stroke, April 1, 2007; 38(4): 1179 - 1184. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Linde, D. Mosier, F. Blecha, and T. Melgarejo Innate immunity and inflammation - New frontiers in comparative cardiovascular pathology Cardiovasc Res, January 1, 2007; 73(1): 26 - 36. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Erridge, C. M. Spickett, and D. J. Webb Non-enterobacterial endotoxins stimulate human coronary artery but not venous endothelial cell activation via Toll-like receptor 2 Cardiovasc Res, January 1, 2007; 73(1): 181 - 189. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Niessner, K. Sato, E. L. Chaikof, I. Colmegna, J. J. Goronzy, and C. M. Weyand Pathogen-Sensing Plasmacytoid Dendritic Cells Stimulate Cytotoxic T-Cell Function in the Atherosclerotic Plaque Through Interferon-{alpha} Circulation, December 5, 2006; 114(23): 2482 - 2489. [Abstract] [Full Text] [PDF] |
||||
![]() |
Z.-q. Yan Regulation of TLR4 Expression Is a Tale About Tail. Arterioscler. Thromb. Vasc. Biol., December 1, 2006; 26(12): 2582 - 2584. [Full Text] [PDF] |
||||
![]() |
F.-Y. Lin, Y.-H. Chen, J.-S. Tasi, J.-W. Chen, T.-L. Yang, H.-J. Wang, C.-Y. Li, Y.-L. Chen, and S.-J. Lin Endotoxin Induces Toll-Like Receptor 4 Expression in Vascular Smooth Muscle Cells via NADPH Oxidase Activation and Mitogen-Activated Protein Kinase Signaling Pathways Arterioscler. Thromb. Vasc. Biol., December 1, 2006; 26(12): 2630 - 2637. [Abstract] [Full Text] [PDF] |
||||
![]() |
W. Koch, P. Hoppmann, A. Pfeufer, A. Schomig, and A. Kastrati Toll-like receptor 4 gene polymorphisms and myocardial infarction: no association in a Caucasian population Eur. Heart J., November 1, 2006; 27(21): 2524 - 2529. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Heidemann, W. Domschke, T. Kucharzik, and C. Maaser Intestinal microvascular endothelium and innate immunity in inflammatory bowel disease: a second line of defense? Infect. Immun., October 1, 2006; 74(10): 5425 - 5432. [Full Text] [PDF] |
||||
![]() |
A. Jaulmes, S. Thierry, B. Janvier, M. Raymondjean, and V. Marechal Activation of sPLA2-IIA and PGE2 production by high mobility group protein B1 in vascular smooth muscle cells sensitized by IL-1{beta} FASEB J, August 1, 2006; 20(10): 1727 - 1729. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. K. Mohammad, M. Morran, B. Slotterbeck, D. W. Leaman, Y. Sun, H. v. Grafenstein, S.-C. Hong, and M. F. McInerney Dysregulated Toll-like receptor expression and signaling in bone marrow-derived macrophages at the onset of diabetes in the non-obese diabetic mouse Int. Immunol., July 1, 2006; 18(7): 1101 - 1113. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Tedgui and Z. Mallat Cytokines in Atherosclerosis: Pathogenic and Regulatory Pathways Physiol Rev, April 1, 2006; 86(2): 515 - 581. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Yilmaz, C. Reiss, A. Weng, I. Cicha, C. Stumpf, A. Steinkasserer, W. G. Daniel, and C. D. Garlichs Differential effects of statins on relevant functions of human monocyte-derived dendritic cells J. Leukoc. Biol., March 1, 2006; 79(3): 529 - 538. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Miyamoto, H. Yumoto, Y. Takahashi, M. Davey, F. C. Gibson III, and C. A. Genco Pathogen-Accelerated Atherosclerosis Occurs Early after Exposure and Can Be Prevented via Immunization Infect. Immun., February 1, 2006; 74(2): 1376 - 1380. [Abstract] [Full Text] [PDF] |
||||
![]() |
F.C. Gibson III, H. Yumoto, Y. Takahashi, H.-H. Chou, and C.A. Genco Innate Immune Signaling and Porphyromonas gingivalis-accelerated Atherosclerosis J. Dent. Res., February 1, 2006; 85(2): 106 - 121. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Yumoto, H.-H. Chou, Y. Takahashi, M. Davey, F. C. Gibson III, and C. A. Genco Sensitization of Human Aortic Endothelial Cells to Lipopolysaccharide via Regulation of Toll-Like Receptor 4 by Bacterial Fimbria-Dependent Invasion Infect. Immun., December 1, 2005; 73(12): 8050 - 8059. [Abstract] [Full Text] [PDF] |
||||
![]() |
X. Yang, D. Coriolan, K. Schultz, D. T. Golenbock, and D. Beasley Toll-Like Receptor 2 Mediates Persistent Chemokine Release by Chlamydia pneumoniae-Infected Vascular Smooth Muscle Cells Arterioscler. Thromb. Vasc. Biol., November 1, 2005; 25(11): 2308 - 2314. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Virmani, F. D. Kolodgie, A. P. Burke, A. V. Finn, H. K. Gold, T. N. Tulenko, S. P. Wrenn, and J. Narula Atherosclerotic Plaque Progression and Vulnerability to Rupture: Angiogenesis as a Source of Intraplaque Hemorrhage Arterioscler. Thromb. Vasc. Biol., October 1, 2005; 25(10): 2054 - 2061. [Abstract] [Full Text] [PDF] |
||||
![]() |
M Rattazzi, E Faggin, B Bertipaglia, and P Pauletto Innate immunity and atherogenesis Lupus, September 1, 2005; 14(9): 747 - 751. [Abstract] [PDF] |
||||
![]() |
H. Methe, J.-O. Kim, S. Kofler, M. Nabauer, and M. Weis Statins Decrease Toll-Like Receptor 4 Expression and Downstream Signaling in Human CD14+ Monocytes Arterioscler. Thromb. Vasc. Biol., July 1, 2005; 25(7): 1439 - 1445. [Abstract] [Full Text] [PDF] |
||||
![]() |
P.S. Olofsson, K. Jatta, D. Wagsater, S. Gredmark, U. Hedin, G. Paulsson-Berne, C. Soderberg-Naucler, G.K. Hansson, and A. Sirsjo The Antiviral Cytomegalovirus Inducible Gene 5/Viperin Is Expressed in Atherosclerosis and Regulated by Proinflammatory Agents Arterioscler. Thromb. Vasc. Biol., July 1, 2005; 25(7): e113 - e116. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. K. Hansson and K. Edfeldt Toll To Be Paid at the Gateway to the Vessel Wall Arterioscler. Thromb. Vasc. Biol., June 1, 2005; 25(6): 1085 - 1087. [Full Text] [PDF] |
||||
![]() |
H. Methe, J.-O. Kim, S. Kofler, M. Weis, M. Nabauer, and J. Koglin Expansion of Circulating Toll-Like Receptor 4-Positive Monocytes in Patients With Acute Coronary Syndrome Circulation, May 24, 2005; 111(20): 2654 - 2661. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. K. Hansson Inflammation, Atherosclerosis, and Coronary Artery Disease N. Engl. J. Med., April 21, 2005; 352(16): 1685 - 1695. [Full Text] [PDF] |
||||
![]() |
G. Caligiuri, S. Kaveri, and A. Nicoletti When Interleukin-18 Conducts, the Preludio Sounds the Same no Matter Who Plays Arterioscler. Thromb. Vasc. Biol., April 1, 2005; 25(4): 655 - 657. [Full Text] [PDF] |
||||
![]() |
A.H. Schoneveld, M.M. Oude Nijhuis, B. van Middelaar, J.D. Laman, D.P.V. de Kleijn, and G. Pasterkamp Toll-like receptor 2 stimulation induces intimal hyperplasia and atherosclerotic lesion development Cardiovasc Res, April 1, 2005; 66(1): 162 - 169. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Z.H. Rittersma, J. A. Kremer Hovinga, K. T. Koch, S. M. Boekholdt, B. E. van Aken, A. Scheepmaker, M. Bax, C. E. Schotborgh, J. J. Piek, J. G.P. Tijssen, et al. Relationship between In Vitro Lipopolysaccharide-Induced Cytokine Response in Whole Blood, Angiographic In-Stent Restenosis, and Toll-Like Receptor 4 Gene Polymorphisms Clin. Chem., March 1, 2005; 51(3): 516 - 521. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Nilsson, G. K. Hansson, and P. K. Shah Immunomodulation of Atherosclerosis: Implications for Vaccine Development Arterioscler. Thromb. Vasc. Biol., January 1, 2005; 25(1): 18 - 28. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Y.L. Zee, H. H. Hegener, J. Gould, and P. M. Ridker Toll-like Receptor 4 Asp299Gly Gene Polymorphism and Risk of Atherothrombosis Stroke, January 1, 2005; 36(1): 154 - 157. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. L. Stoll, G. M. Denning, and N. L. Weintraub Potential Role of Endotoxin as a Proinflammatory Mediator of Atherosclerosis Arterioscler. Thromb. Vasc. Biol., December 1, 2004; 24(12): 2227 - 2236. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. S. Michelsen, T. M. Doherty, P. K. Shah, and M. Arditi TLR Signaling: An Emerging Bridge from Innate Immunity to Atherogenesis J. Immunol., November 15, 2004; 173(10): 5901 - 5907. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. C. Mullaly and P. Kubes Toll Gates and Traffic Arteries: From Endothelial TLR2 to Atherosclerosis Circ. Res., October 1, 2004; 95(7): 657 - 659. [Full Text] [PDF] |
||||
![]() |
S. Dunzendorfer, H.-K. Lee, and P. S. Tobias Flow-Dependent Regulation of Endothelial Toll-Like Receptor 2 Expression Through Inhibition of SP1 Activity Circ. Res., October 1, 2004; 95(7): 684 - 691. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Edfeldt, A. M Bennet, P. Eriksson, J. Frostegard, B. Wiman, A. Hamsten, G. K Hansson, U. d. Faire, and Z.-q. Yan Association of hypo-responsive toll-like receptor 4 variants with risk of myocardial infarction Eur. Heart J., August 2, 2004; 25(16): 1447 - 1453. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. S. Michelsen, M. H. Wong, P. K. Shah, W. Zhang, J. Yano, T. M. Doherty, S. Akira, T. B. Rajavashisth, and M. Arditi Lack of Toll-like receptor 4 or myeloid differentiation factor 88 reduces atherosclerosis and alters plaque phenotype in mice deficient in apolipoprotein E PNAS, July 20, 2004; 101(29): 10679 - 10684. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Marson, R. M. Lawn, and T. Mikita Oxidized Low Density Lipoprotein Blocks Lipopolysaccharide-induced Interferon {beta} Synthesis in Human Macrophages by Interfering with IRF3 Activation J. Biol. Chem., July 2, 2004; 279(27): 28781 - 28788. [Abstract] [Full Text] [PDF] |
||||
![]() |
S.-H. Kim, S. M. Lessner, Y. Sakurai, and Z. S. Galis Cyclophilin A as a Novel Biphasic Mediator of Endothelial Activation and Dysfunction Am. J. Pathol., May 1, 2004; 164(5): 1567 - 1574. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Recalde, M. A. Ostos, E. Badell, A.-L. Garcia-Otin, J. Pidoux, G. Castro, M. M. Zakin, and D. Scott-Algara Human Apolipoprotein A-IV Reduces Secretion of Proinflammatory Cytokines and Atherosclerotic Effects of a Chronic Infection Mimicked by Lipopolysaccharide Arterioscler. Thromb. Vasc. Biol., April 1, 2004; 24(4): 756 - 761. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Pasterkamp, Z. S. Galis, and D. P.V. de Kleijn Expansive Arterial Remodeling: Location, Location, Location Arterioscler. Thromb. Vasc. Biol., April 1, 2004; 24(4): 650 - 657. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Li, T. Ha, J. Kelley, X. Gao, Y. Qiu, R. L Kao, W. Browder, and D. L Williams Modulating Toll-like receptor mediated signaling by (1->3)-{beta}-D-glucan rapidly induces cardioprotection Cardiovasc Res, February 15, 2004; 61(3): 538 - 547. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. C.G. Hollestelle, M. R. de Vries, J. K. van Keulen, A. H. Schoneveld, A. Vink, C. F. Strijder, B. J. van Middelaar, G. Pasterkamp, P. H.A. Quax, and D. P.V. de Kleijn Toll-Like Receptor 4 Is Involved in Outward Arterial Remodeling Circulation, January 27, 2004; 109(3): 393 - 398. [Abstract] [Full Text] [PDF] |
||||