Autoimmunological features in inflammatory cardiomyopathy

Kallwellis-Opara, Angela; Dörner, Andrea; Poller, Wolfgang; Noutsias, Michel; Kühl, Uwe; Schultheiss, Heinz‐Peter; Pauschinger, M.

doi:10.1007/s00392-007-0524-x

Cited by 55 publications

(43 citation statements)

References 148 publications

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“…The life expectancy after diagnosis of DCM is only 50% at 4 yr. Chronic myocardial inflammation, particularly following viral myocarditis, has been termed inflammatory DCM (iDCM) by the World Health Organization's classification of cardiomyopathies (35,44). Coxsackievirus B3 (CVB3), a common enterovirus, is a major cause of myocarditis leading to iDCM in Western populations (9,10,20).…”

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confidence: 99%

TLR3 deficiency induces chronic inflammatory cardiomyopathy in resistant mice following coxsackievirus B3 infection: role for IL-4

Abston

Coronado

Bucek

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

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Recent findings indicate that TLR3 polymorphisms increase susceptibility to enteroviral myocarditis and inflammatory dilated cardiomyopathy (iDCM) in patients. TLR3 signaling has been found to inhibit coxsackievirus B3 (CVB3) replication and acute myocarditis in mouse models, but its role in the progression from myocarditis to iDCM has not been previously investigated. In this study we found that TLR3 deficiency increased acute ( P = 5.9 × 10−9) and chronic ( P = 6.0 × 10−7) myocarditis compared with WT B6.129, a mouse strain that is resistant to chronic myocarditis and iDCM. Using left ventricular in vivo hemodynamic assessment, we found that TLR3-deficient mice developed progressively worse chronic cardiomyopathy. TLR3 deficiency significantly increased viral replication in the heart during acute myocarditis from day 3 through day 12 after infection, but infectious virus was not detected in the heart during chronic disease. TLR3 deficiency increased cytokines associated with a T helper (Th)2 response, including IL-4 ( P = 0.03), IL-10 ( P = 0.008), IL-13 ( P = 0.002), and TGF-β1 ( P = 0.005), and induced a shift to an immunoregulatory phenotype in the heart. However, IL-4-deficient mice had improved heart function during acute CVB3 myocarditis by echocardiography and in vivo hemodynamic assessment compared with wild-type mice, indicating that IL-4 impairs cardiac function during myocarditis. IL-4 deficiency increased regulatory T-cell and macrophage populations, including FoxP3+ T cells ( P = 0.005) and Tim-3+ macrophages ( P = 0.004). Thus, TLR3 prevents the progression from myocarditis to iDCM following CVB3 infection by reducing acute viral replication and IL-4 levels in the heart.

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confidence: 99%

TLR3 deficiency induces chronic inflammatory cardiomyopathy in resistant mice following coxsackievirus B3 infection: role for IL-4

Abston

Coronado

Bucek

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

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“…1 Inflammatory cardiomyopathy often results from infection-triggered myocarditis and is characterized by impaired cardiac contractility, ventricular dilation, and progressive myocardial fibrosis. 2,3 Many viruses but also bacteria, parasites, drugs, and systemic diseases are supposed to trigger cardiac inflammation.…”

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confidence: 99%

Myeloid Differentiation Factor-88/Interleukin-1 Signaling Controls Cardiac Fibrosis and Heart Failure Progression in Inflammatory Dilated Cardiomyopathy

Błyszczuk

Kania

Dieterle

et al. 2009

Circulation Research

107

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“…A pathogen-induced breakdown in the control mechanisms protecting against autoimmune reactions through both the presentation of normal self-antigens and bystander activation leads to the formation of autoreactive antibodies and T cells. The auto-reactive antibodies interact directly with heart tissue, altering signal transduction or complement activation, whereas T-cell-mediated mechanisms include direct attack by cytotoxic T cells or indirect effects of cytotoxic cytokines released by stimulated T cells or macrophages (Kallwellis-Opara et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Transcriptome network analysis of potential candidate genes for heart failure

Chen¹,

Wang²,

Zeng³

2013

Genet. Mol. Res.

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ABSTRACT. The purpose of this study was to examine the hypothesis that a transcriptome network can be developed through a set of transcription factors regulated by the expression of various genes induced by dilated cardiomyopathy can be identified and modulated to respond to heart failure. We searched for significant pathways related to dilated cardiomyopathy using the GSE4172 microarray data to identify potential genes related to heart failure. We mapped differentially expressed genes to pathways and constructed a regulation network to investigate the regulatory relationships between transcription factors and pathways. Some transcription factors and target genes in the networks have been clearly linked to heart failure in previous studies. We also found new transcription factors and target genes, such as CCAAT/ enhancer-binding protein delta and JunB, responsible for inflammatory cardiomyopathy. Transcriptome network analysis was useful in the identification of candidate genes in heart failure. This method is well suited for microarray data and therefore is proposed as a powerful tool in the search for new pathways related to disease.

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Autoimmunological features in inflammatory cardiomyopathy

Cited by 55 publications

References 148 publications

TLR3 deficiency induces chronic inflammatory cardiomyopathy in resistant mice following coxsackievirus B3 infection: role for IL-4

TLR3 deficiency induces chronic inflammatory cardiomyopathy in resistant mice following coxsackievirus B3 infection: role for IL-4

Myeloid Differentiation Factor-88/Interleukin-1 Signaling Controls Cardiac Fibrosis and Heart Failure Progression in Inflammatory Dilated Cardiomyopathy

Transcriptome network analysis of potential candidate genes for heart failure

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