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[PMID]: | 28912259 |
[Au] Autor: | Tschöpe C; Müller I; Xia Y; Savvatis K; Pappritz K; Pinkert S; Lassner D; Heimesaat MM; Spillmann F; Miteva K; Bereswill S; Schultheiss HP; Fechner H; Pieske B; Kühl U; Van Linthout S |
[Ad] Endereço: | From the Department of Cardiology and Pneumology, Charité-Universitätsmedizin Berlin, Campus Virchow Klinikum, Germany (C.T., Y.X., K.S., F.S., B.P., U.K., S.V.L.); DZHK (German Center for Cardiovascular Research), partner site Berlin, Germany (C.T., I.M., K.P., B.P., S.V.L.); Berlin-Brandenburg Cen |
[Ti] Título: | NOD2 (Nucleotide-Binding Oligomerization Domain 2) Is a Major Pathogenic Mediator of Coxsackievirus B3-Induced Myocarditis. |
[So] Source: | Circ Heart Fail;10(9), 2017 Sep. | [Is] ISSN: | 1941-3297 |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | BACKGROUND: The cytoplasmatic pattern recognition receptor, NOD2 (nucleotide-binding oligomerization domain 2), belongs to the innate immune system and is among others responsible for the recognition of single-stranded RNA. With Coxsackievirus B3 (CVB3) being a single-stranded RNA virus, and the recent evidence that the NOD2 target, NLRP3 (NOD-like receptor family, pyrin domain containing 3) is of importance in the pathogenesis of CVB3-induced myocarditis, we aimed to unravel the role of NOD2 in CVB3-induced myocarditis. METHODS AND RESULTS: Endomyocardial biopsy NOD2 mRNA expression was higher in CVB3-positive patients compared with patients with myocarditis but without evidence of persistent CVB3 infection. Left ventricular NOD2 mRNA expression was also induced in CVB3-induced myocarditis versus healthy control mice. NOD2 knockdown mice were rescued from the detrimental CVB3-mediated effects as shown by a reduced cardiac inflammation (less cardiac infiltrates and suppression of proinflammatory cytokines), cardiac fibrosis, apoptosis, lower CAR (Coxsackievirus and adenovirus receptor) expression and CVB3 copy number, and an improved left ventricular function in NOD2 CVB3 mice compared with wild-type CVB3 mice. In agreement, NOD2 decreased the CVB3-induced inflammatory response, CVB3 copy number, and apoptosis in vitro. NOD2 was further associated with a reduction in CVB3-induced NLRP3 expression and activity as evidenced by lower ASC (apoptosis-associated speck-like protein containing a CARD) expression, caspase 1 activity, or IL-1ß (interleukin-1ß) protein expression under in vivo and in vitro CVB3 conditions. CONCLUSIONS: NOD2 is an important mediator in the viral uptake and inflammatory response during the pathogenesis of CVB3 myocarditis. |
[Mh] Termos MeSH primário: |
Infecções por Coxsackievirus/metabolismo Enterovirus Humano B/metabolismo Miocardite/metabolismo Miocárdio/metabolismo Proteína Adaptadora de Sinalização NOD2/metabolismo
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[Mh] Termos MeSH secundário: |
Animais Apoptose Proteínas Reguladoras de Apoptose/metabolismo Proteínas Adaptadoras de Sinalização CARD Estudos de Casos e Controles Caspase 1/metabolismo Linhagem Celular Infecções por Coxsackievirus/imunologia Infecções por Coxsackievirus/prevenção & controle Infecções por Coxsackievirus/virologia Modelos Animais de Doenças Enterovirus Humano B/genética Enterovirus Humano B/imunologia Predisposição Genética para Doença Interações Hospedeiro-Patógeno Seres Humanos Interleucina-1beta/metabolismo Masculino Camundongos Endogâmicos C57BL Camundongos Knockout Miocardite/imunologia Miocardite/prevenção & controle Miocardite/virologia Miocárdio/imunologia Miocárdio/patologia Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo Proteína Adaptadora de Sinalização NOD2/deficiência Proteína Adaptadora de Sinalização NOD2/genética Fenótipo Interferência de RNA Transdução de Sinais Transfecção Regulação para Cima
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[Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (Apoptosis Regulatory Proteins); 0 (CARD Signaling Adaptor Proteins); 0 (Card15 protein, mouse); 0 (IL1B protein, mouse); 0 (Interleukin-1beta); 0 (NLR Family, Pyrin Domain-Containing 3 Protein); 0 (NOD2 protein, human); 0 (Nlrp3 protein, mouse); 0 (Nod2 Signaling Adaptor Protein); 0 (Pycard protein, mouse); EC 3.4.22.36 (Caspase 1) |
[Em] Mês de entrada: | 1709 |
[Cu] Atualização por classe: | 171116 |
[Lr] Data última revisão:
| 171116 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 170916 |
[St] Status: | MEDLINE |
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