Inhibition of urokinase-type plasminogen activator or matrix metalloproteinases prevents cardiac injury and dysfunction during viral myocarditis
| العنوان: | Inhibition of urokinase-type plasminogen activator or matrix metalloproteinases prevents cardiac injury and dysfunction during viral myocarditis |
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| المؤلفون: | Peter Carmeliet, Johan Neyts, Heinz-Peter Schultheiss, Fangye Gao, Stephane Heymans, Melissa Swinnen, Raimund Torpai, Frans Van de Werf, Yigal M. Pinto, Armando M. De Palma, Angela Kallwellis-Opara, Susanne Rutschow, Andy Baker, Matthias Pauschinger, E. Padalko, Davy Vanhoutte |
| المساهمون: | Cardiology |
| المصدر: | Circulation, 114(6), 565-573. Lippincott Williams and Wilkins |
| سنة النشر: | 2006 |
| مصطلحات موضوعية: | Male, Myocarditis, Viral Myocarditis, Matrix metalloproteinase inhibitor, Cardiac fibrosis, Matrix Metalloproteinase Inhibitors, chemistry.chemical_compound, Mice, Physiology (medical), Plasminogen Activator Inhibitor 1, medicine, Enterovirus Infections, Animals, Fibrinolysin, RNA, Messenger, Urokinase, Mice, Knockout, Tissue Inhibitor of Metalloproteinase-1, business.industry, Myocardium, virus diseases, Heart, medicine.disease, Endomyocardial Fibrosis, Urokinase-Type Plasminogen Activator, Matrix Metalloproteinases, Enterovirus B, Human, Mice, Inbred C57BL, chemistry, Gene Expression Regulation, Heart failure, Plasminogen activator inhibitor-1, Immunology, cardiovascular system, Cancer research, Cytokines, Female, Cardiology and Cardiovascular Medicine, business, Plasminogen activator, medicine.drug, Dilatation, Pathologic |
| الوصف: | Background—Acute viral myocarditis is an important cause of cardiac failure in young adults for which there is no effective treatment apart from general heart failure therapy. The present study tested the hypothesis that increased expression of the proteinases urokinase-type plasminogen activator (uPA) and matrix metalloproteinases (MMPs) is implicated in cardiac inflammation, injury, and subsequent failure during Coxsackievirus-B3 (CVB3)–induced myocarditis.Methods and Results—First, we showed increased expression and activity of uPA and MMP-9 in wild-type mice at 7 days of CVB3-induced myocarditis. Targeted deletion of uPA, which resulted in reduced MMP activity and cytokine expression or inhibition of MMPs by adenoviral gene overexpression of tissue inhibitor of metalloproteinases-1, decreased cardiac inflammation and reduced myocardial necrosis at 7 days and decreased cardiac fibrosis at 35 days after CVB3 infection. Importantly, loss of uPA or MMP activity prevented CVB3-induced cardiac dilatation and dysfunction, as determined by serial echocardiography.Conclusions—Loss of uPA or MMP activity reduces the cardiac inflammatory response after CVB3 infection, thereby protecting against cardiac injury, dilatation, and failure during CVB3-induced myocarditis. |
| تدمد: | 1524-4539 0009-7322 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::549e0441f6ed0deff7e06acdc0e5a7ce https://pubmed.ncbi.nlm.nih.gov/16880329 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....549e0441f6ed0deff7e06acdc0e5a7ce |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15244539 00097322 |
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