(Circulation. 2002;105:1158.)
© 2002 American Heart Association, Inc.
Brief Rapid Communications |
Expression of Toll-Like Receptors in Human Atherosclerotic Lesions
A Possible Pathway for Plaque Activation
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
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G. Pinhal-Enfield, M. Ramanathan, G. Hasko, S. N. Vogel, A. L. Salzman, G.-J. Boons, and S. J. Leibovich An Angiogenic Switch in Macrophages Involving Synergy between Toll-Like Receptors 2, 4, 7, and 9 and Adenosine A2A Receptors Am. J. Pathol., August 1, 2003; 163(2): 711 - 721. [Abstract] [Full Text] [PDF]
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N. Mackman How Do Oxidized Phospholipids Inhibit LPS Signaling? Arterioscler Thromb Vasc Biol, July 1, 2003; 23(7): 1133 - 1136. [Full Text] [PDF]
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G.D. Norata, A. Pirillo, E. Callegari, A. Hamsten, A.L. Catapano, and P. Eriksson Gene expression and intracellular pathways involved in endothelial dysfunction induced by VLDL and oxidised VLDL Cardiovasc Res, July 1, 2003; 59(1): 169 - 180. [Abstract] [Full Text] [PDF]
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S. M. Boekholdt, W. R.P. Agema, R. J.G. Peters, A. H. Zwinderman, E. E. van der Wall, P. H. Reitsma, J. J.P. Kastelein, and J. W. Jukema Variants of Toll-Like Receptor 4 Modify the Efficacy of Statin Therapy and the Risk of Cardiovascular Events Circulation, May 20, 2003; 107(19): 2416 - 2421. [Abstract] [Full Text] [PDF]
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Y. I. Miller, S. Viriyakosol, C. J. Binder, J. R. Feramisco, T. N. Kirkland, and J. L. Witztum Minimally Modified LDL Binds to CD14, Induces Macrophage Spreading via TLR4/MD-2, and Inhibits Phagocytosis of Apoptotic Cells J. Biol. Chem., January 10, 2003; 278(3): 1561 - 1568. [Abstract] [Full Text] [PDF]
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A. Vink, A. H. Schoneveld, J. J. van der Meer, B. J. van Middelaar, J. P.G. Sluijter, M. B. Smeets, P. H.A. Quax, S. K. Lim, C. Borst, G. Pasterkamp, et al. In Vivo Evidence for a Role of Toll-Like Receptor 4 in the Development of Intimal Lesions Circulation, October 8, 2002; 106(15): 1985 - 1990. [Abstract] [Full Text] [PDF]
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Q. Xu Role of Heat Shock Proteins in Atherosclerosis Arterioscler Thromb Vasc Biol, October 1, 2002; 22(10): 1547 - 1559. [Abstract] [Full Text] [PDF]
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G. K. Hansson, P. Libby, U. Schonbeck, and Z.-Q. Yan Innate and Adaptive Immunity in the Pathogenesis of Atherosclerosis Circ. Res., August 23, 2002; 91(4): 281 - 291. [Abstract] [Full Text] [PDF]
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