Mechanisms of Disease: Toll-like Receptors in Cardiovascular Disease

Table 1.

A Summary of the Genetic Analyses of Polymorphisms in the TLR Genes

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Author(s)

Stefan Frantz

Cardiologist, University of WÃ¼rzburg, Medizinische Klinik und Poliklinik I, Herzkreislauf-Zentrum, WÃ¼rzburg, Germany

Disclosures

Disclosure: Stefan Frantz has disclosed no relevant financial relationships.

Georg Ertl

Chair, Internal Medicine; Director, University of WÃ¼rzburg, Medizinische Klinik und Poliklinik I, Herzkreislauf-Zentrum, WÃ¼rzburg, Germany

Disclosures

Disclosure: Georg Ertl has disclosed no relevant financial relationships.

Johann Bauersachs

Consultant, University of WÃ¼rzburg, Medizinische Klinik und Poliklinik I, Herzkreislauf-Zentrum, WÃ¼rzburg, Germany

Disclosures

Disclosure: Johann Bauersachs has disclosed no relevant financial relationships.

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Summary and Introduction

Summary

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.

Introduction

Most microorganisms encountered by healthy individuals are recognized initially by defense mechanisms that are not antigen-specific, a response mediated by the so-called innate immune system. In contrast to adaptive immunity, in which specific antigen receptors are generated by somatic hypermutation and selection, in the innate immune system germline-encoded receptor proteins recognize specific patterns that are shared by groups of pathogens, but not the host. These receptorsâ€’'pattern recognition receptors' (PRRs)â€’ detect pathogen-associated molecular patterns (PAMPs) that remain largely unvaried, such as lipopolysaccharide found on the cell surface of Gram-negative bacteria, or double-stranded RNA present in viruses.^[1â€“3]

In 1997, vertebrate homologs of the Drosophila spp. transmembrane PRR 'Toll' were identified and termed the 'Toll-like receptors' (TLRs).^[4] To date, 11 human and 13 mouse TLRs have been cloned.^[3] TLRs have since been shown to be central to the innate immune response. Here, we aim to review the exciting field of TLR activation in the cardiovascular system, and the role individual TLR family members could have in the pathophysiology of cardiovascular diseases.