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Cited by 53Viral Infections and Immunology ResearchCardiac Fibrosis and RemodelingImmune Response and Inflammation

Toll-like receptor 4 is expressed with enteroviral replication in myocardium from patients with dilated cardiomyopathy

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Satoh, Mamoru, Nakamura, Motoyuki, Akatsu, Tomonari, Shimoda, Yudai, Segawa, Ikuo, Hiramori, Katsuhiko·2004·Laboratory Investigation
DOI 10.1038/labinvest.3700031
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Abstract

Expressions of innate immune response proteins, most notably proinflammatory cytokines, against enteroviral (EV) infection have been documented in the heart of human dilated cardiomyopathy (DCM). Toll-like receptor 4 (TLR4) activates signaling pathways leading to the expression of proinflammatory cytokines implicated the etiology of DCM. We sought to determine whether EV replication activates TLR4-dependent immune response in myocardium obtained from patients with DCM. Endomyocardial biopsy tissues were obtained from 56 patients with DCM and 10 controls. Levels of plus- and minus-strand EV RNA and TLR4 mRNA were measured by real-time RT-PCR. Immunohistochemical analysis was performed to identify the cellular source of EV capsid protein VP1 and TLR4. Both plus- and minus-strand EV RNA were detected in 19 DCM patients (34%). Neither strand of EV RNA was detected in controls. TLR4 mRNA levels were higher in DCM patients than in controls (P<0.001). A positive correlation was found between TLR4 levels and each strand type of EV RNA in EV RNA-positive patients (plus-strand vs TLR4: r=0.69, P<0.001; minus-strand vs TLR4: r=0.65, P=0.002). VP1/TLR4 double staining showed extensive colocalization of VP1 and TLR4 proteins in cytoplasm of cardiac myocytes in myocardium obtained from DCM patients. EV RNA-positive patients showed lower systolic function and larger ventricular volume compared with EV RNA-negative patients left ventricular ejection fraction (LVEF): P=0.002; left ventricular end-systolic diameter (LVESD): P=0.004). The DCM subgroup with high TLR4 levels showed lower LVEF and larger LVESD than the subgroup with TLR4 levels (both P<0.001). This study suggests that myocardial expression of TLR4 associates with EV replication in human DCM. EV RNA and TLR4 mRNA levels may correlate with LV dysfunction in DCM. The expression of TLR4 against EV replication may be involved in the pathogenesis of DCM.

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  • TLR4 is expressed in the heart of patients with myocarditis and DCM.

    “TLR4 was also found to be expressed in the heart of patients with myocarditis and DCM. 166,167”

    From COVID-19, Myocarditis and Pericarditis (2023) · cites this paper as [167]

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Authors
Satoh, M., Nakamura, M., Akatsu, T., Shimoda, Y., Segawa, I., & Hiramori, K.
Affiliations
Iwate Medical University (JP)
Corresponding author
Satoh, Mamoru
ORCID
Venue
Laboratory Investigation
Publisher
Elsevier BV
Published
2004-02
Volume
84
Issue
2
Pages
173-181
ISSN
0023-6837 (ISSN-L)
DOI
10.1038/labinvest.3700031
OpenAlex
W2020110663
Cited by
53
References
34
Citations by year
2026: 1 · 2025: 1 · 2023: 7 · 2021: 1 · 2020: 3 · 2019: 2 · 2018: 1 · 2017: 1 · 2016: 1 · 2015: 2 · 2014: 3 · 2013: 3 · 2012: 2
FWCI
2.86
Type
journal article
Language
en
Open access
Licence
Locations
  • Laboratory Investigation (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Viral Infections and Immunology Research
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords
TLR4, dilated cardiomyopathy, enterovirus replication, myocardium, VP1 capsid protein, innate immune response, inflammatory cytokines, left ventricular dysfunction, endomyocardial biopsy, viral pathogenesis
MeSH terms
Adolescent, Adult, Aged, Biopsy, Cardiomyopathy, Dilated, Enterovirus Infections, Enterovirus, Female, Humans, Immunoenzyme Techniques, Male, Membrane Glycoproteins, Middle Aged, Myocardium, Receptors, Cell Surface, RNA, Messenger, RNA, Viral, Virus Replication, Signal Transduction, Ventricular Dysfunction, Left, Myocytes, Cardiac, Capsid Proteins, Toll-Like Receptors, Toll-Like Receptor 4

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