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Mechanisms of Disease: Toll-like receptors in cardiovascular disease

Nature Clinical Practice Cardiovascular Medicine volume 4, pages 444–454 (2007)Cite this article

Abstract

The innate immune system detects highly conserved, relatively invariant structural motifs of pathogens. Toll-like receptors (TLRs) have been identified as the primary innate immune receptors. TLRs distinguish between different patterns of pathogens and activate a rapid innate immune response; however, TLRs can also be activated by host-derived molecules. In addition to being expressed in immune cells, TLRs are expressed in other tissues, such as those of the cardiovascular system. TLRs could, therefore, be a key link between cardiovascular disease development and the immune system. Indeed, evidence that TLR activation contributes to the development and progression of atherosclerosis, cardiac dysfunction in sepsis, and congestive heart failure, is convincing. Although much has been learned about TLR activation in cellular components of the cardiovascular system, the role individual TLR family members have in the pathophysiology of cardiovascular diseases and hence in clinical practice remains to be defined. Here we review the rapid progress that has been made in this field, which has improved our understanding of vascular as well as myocardial TLR function in basic and clinical science.

Key Points

  • The innate immune system detects evolutionary highly conserved structural motifs of pathogens; Toll-like receptors (TLRs) are a family of pattern recognition receptors with central importance in the innate immune response

  • TLRs are expressed in vascular as well as myocardial cells

  • In myocardial diseases TLRs might be important in septic and toxic cardiomyopathy as well as hypertrophy and heart failure; this evidence comes almost exclusively from basic science data

  • A considerable amount of evidence links the pathogenesis of atherosclerosis with TLR signaling, through association studies of TLR4 polymorphisms and myocardial infarction risk, direct activation of TLRs after myocardial infarction, and experimental in vivo studies demonstrating decreased atherosclerosis development in TLR knockout mice

  • The function of TLRs in clinical practice remains to be defined

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Figure 1: The Toll-like receptor signaling pathway
Figure 2: Aortic atherosclerotic lesions in mice exposed to the synthetic Toll-like receptor 2 agonist Pam3
Figure 3: Toll-like receptor 4 expression in rat, murine and human myocardium
Figure 4: Nuclear factor κ B activation in the heart after ischemic injury

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Acknowledgements

Charles P Vega, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape–accredited continuing medical education activity associated with this article.

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Authors and Affiliations

  1. Department of Internal Medicine I, S Frantz is a Cardiologist, G Ertl is Chair of Internal Medicine and Director, and J Bauersachs is a Senior Cardiologist, at the University of Würzburg, Herzkreislauf-Zentrum, Würzburg, Germany.,

    Stefan Frantz, Georg Ertl & Johann Bauersachs

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  1. Stefan Frantz
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Correspondence to Stefan Frantz.

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Frantz, S., Ertl, G. & Bauersachs, J. Mechanisms of Disease: Toll-like receptors in cardiovascular disease. Nat Rev Cardiol 4, 444–454 (2007). https://doi.org/10.1038/ncpcardio0938

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