Myocardial Expression of Fas and Recovery of Left Ventricular Function in Patients With Recent-Onset Cardiomyopathy

Sheppard, Richard; Bedi, Maninder; Kubota, Takeshi; Semigran, Marc J.; Dec, William G.; Holubkov, Richard; Feldman, Arthur M.; Rosenblum, Warren D.; McTiernan, Charles F.; McNamara, Dennis M.

doi:10.1016/j.jacc.2005.05.067

Cited by 55 publications

(44 citation statements)

References 23 publications

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“…Recent clinical studies have indicated that alpha interferon (IFN-␣) (11,21,35,36) and IFN-␤ (29) can reduce the severity of viral myocarditis, inhibiting viral replication and improving cardiac function. Nonetheless, viral myocarditis remains a disease without reliable treatment, and the prognosis remains poor for more than half of patients presenting with clinical symptoms (45).…”

mentioning

confidence: 99%

Basal Expression Levels of IFNAR and Jak-STAT Components Are Determinants of Cell-Type-Specific Differences in Cardiac Antiviral Responses

Zurney¹,

Howard

Sherry

2007

J Virol

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Viral myocarditis is an important human disease, and reovirus-induced murine myocarditis provides an excellent model system for study. Cardiac myocytes, like neurons in the central nervous system, are not replenished, yet there is no cardiac protective equivalent to the blood-brain barrier. Thus, cardiac myocytes may have evolved a unique antiviral response relative to readily replenished cell types, such as cardiac fibroblasts. Our previous comparisons of these two cell types revealed a conundrum: reovirus T3D induces more beta-interferon (IFN-␤) mRNA in cardiac myocytes, yet there is a greater induction of IFN-stimulated genes (ISGs) in cardiac fibroblasts. Here, we investigated possible underlying molecular determinants. We found that greater basal expression of IFN-␤ in cardiac myocytes results in greater basal activated nuclear STAT1 and STAT2 and greater basal ISG mRNA expression and provides greater basal antiviral protection relative to cardiac fibroblasts. Conversely, cardiac fibroblasts express greater basal IFN-␣/␤ receptor 1 (IFNAR1) and greater basal cytoplasmic Jak1, Tyk2, STAT2, and IRF9, leading to a greater increase in reovirus T3D-or IFN-induced nuclear activated STAT1 and STAT2 and greater induction of ISGs for a greater IFN-induced antiviral protection relative to cardiac myocytes. Our results suggest that high basal IFN-␤ expression in cardiac myocytes prearms this vulnerable, nonreplenishable cell type, while high basal expression of IFNAR1 and latent Jak-STAT components in adjacent cardiac fibroblasts renders these cells more responsive to IFN and prevents them from inadvertently serving as a reservoir for viral replication and spread to cardiac myocytes. These studies provide the first indication of an integrated network of cell-type-specific innate immune components for organ protection.

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mentioning

confidence: 99%

Basal Expression Levels of IFNAR and Jak-STAT Components Are Determinants of Cell-Type-Specific Differences in Cardiac Antiviral Responses

Zurney¹,

Howard

Sherry

2007

J Virol

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“…17 A few serologic and imaging biomarkers have been associated with poor clinical outcome. For example, relatively high serum levels of Fas ligand and interleukin-10 may predict an increased risk of death 18,19 although these assays are not widely available.…”

Section: Diagnosismentioning

confidence: 99%

Myocarditis-A Quick Review

Prasad¹,

Kumar²

2017

IOSR JDMS

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“…2 is a relevant cause of heart failure leading to increased morbidity and mortality (1,2). The etiology of this disease is currently under intense investigation.…”

Section: Dilated Cardiomyopathy (Dcm)mentioning

confidence: 99%

Variants of Toll-like Receptor 4 Predict Cardiac Recovery in Patients with Dilated Cardiomyopathy

Riad

Schwabedissen

Weitmann

et al. 2012

Journal of Biological Chemistry

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Background:The impact of polymorphisms of TLR4 on left ventricular performance in DCM patients is unknown. Results: Patients carrying TLR4 variants had reduced improvement of left ventricular function and dilation and no increase in NT-pro-BNP level at follow up when compared with wild type genes. Conclusion: TLR4 variants predict cardiac recovery in DCM.Significance: This is the first study to investigate the impact of an innate immune receptor on cardiac recovery in human DCM.

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Myocardial Expression of Fas and Recovery of Left Ventricular Function in Patients With Recent-Onset Cardiomyopathy

Abstract: In cardiomyopathy of recent onset, increased expression of Fas and TNFR1 was associated with minimal recovery of LV function. Apoptosis limits myocardial recovery, and represents a potential target for therapeutic intervention.

Cited by 55 publications

References 23 publications

Basal Expression Levels of IFNAR and Jak-STAT Components Are Determinants of Cell-Type-Specific Differences in Cardiac Antiviral Responses

Basal Expression Levels of IFNAR and Jak-STAT Components Are Determinants of Cell-Type-Specific Differences in Cardiac Antiviral Responses

Myocarditis-A Quick Review

Variants of Toll-like Receptor 4 Predict Cardiac Recovery in Patients with Dilated Cardiomyopathy

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