Soluble Tumor Necrosis Factor Receptor Abrogates Myocardial Inflammation but Not Hypertrophy in Cytokine-Induced Cardiomyopathy
| Autor: | Toru Kubota, Charles F. McTiernan, Christina Bruton, Toshiaki Kadokami, Masayuki Miyagishima, Paul D. Robbins, Arthur M. Feldman, Virginia J. Sanders, George S. Bounoutas |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Cardiomyopathy
Dilated medicine.medical_specialty medicine.medical_treatment Genetic Vectors Cardiomyopathy Down-Regulation Enzyme-Linked Immunosorbent Assay Mice Transgenic Calcium-Transporting ATPases Receptors Tumor Necrosis Factor Adenoviridae Etanercept Muscle hypertrophy Mice Downregulation and upregulation Physiology (medical) Internal medicine medicine Animals Receptor Myosin Heavy Chains business.industry Monocyte Calcium-Binding Proteins Intercellular Adhesion Molecule-1 medicine.disease Immunohistochemistry Phospholamban Myocarditis Sarcoplasmic Reticulum medicine.anatomical_structure Endocrinology Cytokine Immunoglobulin G Tumor necrosis factor alpha Cardiology and Cardiovascular Medicine business Viral Fusion Proteins Interleukin-1 |
| Zdroj: | Circulation. 101:2518-2525 |
| ISSN: | 1524-4539 0009-7322 |
| DOI: | 10.1161/01.cir.101.21.2518 |
| Popis: | Background —Transgenic mice with cardiac-specific overexpression of tumor necrosis factor (TNF)-α develop dilated cardiomyopathy. The present study was designed to evaluate therapeutic effects of adenovirus-mediated neutralization of TNF-α on this model. Methods and Results —An adenovirus encoding the 55-kDa TNF receptor–IgG fusion protein (AdTNFRI) was injected intravenously into 6-week-old transgenic mice, which resulted in high levels of TNFRI in both plasma and myocardium. AdTNFRI did not reverse cardiomegaly but abrogated myocardial inflammation. Furthermore, AdTNFRI blocked the myocardial expression of intercellular adhesion molecule-1 and downstream cytokines, including interleukin-1β and monocyte chemotactic protein-1. Downregulation of α-myosin heavy chain was restored by the treatment, whereas upregulation of β-myosin heavy chain was not reversed. In contrast, the downregulation of sarcoplasmic reticulum Ca 2+ -ATPase and phospholamban was normalized by AdTNFRI. Echocardiographic measurements showed that left ventricular end-systolic diameter was significantly larger in transgenic mice than in control mice, and this increase was reversed by the AdTNFRI treatment. However, left ventricular wall thickening was not reversed. Conclusions —These results suggest that anti-TNF therapy may hold promise in the treatment of end-stage heart failure. |
| Databáze: | OpenAIRE |
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