Research article summary (published 15 Sep 2009):

Myeloid differentiation factor-88/interleukin-1 signaling controls cardiac fibrosis and heart failure progression in inflammatory dilated cardiomyopathy.

Full Abstract

RATIONALE: The myeloid differentiation factor (MyD)88/interleukin (IL)-1 axis activates self-antigen-presenting cells and promotes autoreactive CD4(+) T-cell expansion in experimental autoimmune myocarditis, a mouse model of inflammatory heart disease. OBJECTIVE: The aim of this study was to determine the role of MyD88 and IL-1 in the progression of acute myocarditis to an end-stage heart failure. METHODS AND RESULTS: Using alpha-myosin heavy chain peptide (MyHC-alpha)-loaded, activated dendritic cells, we induced myocarditis in wild-type and MyD88(-/-) mice with similar distributions of heart-infiltrating cell subsets and comparable CD4(+) T-cell responses. Injection of complete Freund's adjuvant (CFA) or MyHC-alpha/CFA into diseased mice promoted cardiac fibrosis, induced ventricular dilation, and impaired heart function in wild-type but not in MyD88(-/-) mice. Experiments with chimeric mice confirmed the bone marrow origin of the fibroblasts replacing inflammatory infiltrates and showed that MyD88 and IL-1 receptor type I signaling on bone marrow-derived cells was critical for development of cardiac fibrosis during progression to heart failure. CONCLUSIONS: Our findings indicate a critical role of MyD88/IL-1 signaling in the bone marrow compartment in postinflammatory cardiac fibrosis and heart failure and point to novel therapeutic strategies against inflammatory cardiomyopathy.

Author information

Author/s: Blyszczuk, Przemyslaw (P); Kania, Gabriela (G); Dieterle, Thomas (T); Marty, Rene R (RR); Valaperti, Alan (A); Berthonneche, Corinne (C); Pedrazzini, Thierry (T); Berger, Christoph T (CT); Dirnhofer, Stephan (S); Matter, Christian M (CM); Penninger, Josef M (JM); Lüscher, Thomas F (TF); Eriksson, Urs (U);

Affiliation: Department of Cardiology, University Hospital, Zurich, Switzerland. przemyslaw.blyszczuk(-atsign-)access.uzh.ch

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Circulation research (Circ Res), published in United States. (Language: eng)

Reference: 2009-Oct; vol 105 (issue 9) : pp 912-20

Dates: Created 2009/10/23; Completed 2009/11/05;

PMID: 19762681, status: MEDLINE (last retrieval date: 11/5/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals Autoimmunity Bone Marrow Transplantation CD4-Positive T-Lymphocytes - immunology Cardiomyopathy, Dilated - immunology; pathology; physiopathology Cells, Cultured Dendritic Cells - immunology; transplantation Disease Models, Animal Disease Progression Fibroblasts - immunology Fibrosis Freund's Adjuvant Green Fluorescent Proteins - genetics Heart Failure - immunology; pathology; physiopathology Immunity, Innate

Immunity, Innate Interleukin-1beta - metabolism Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Myeloid Differentiation Factor 88 - deficiency; genetics; metabolism Myocarditis - complications; immunology; pathology; physiopathology Myocardium - immunology; pathology Myosin Heavy Chains - immunology Phenotype Receptors, Interleukin-1 Type I - genetics; metabolism Signal Transduction Transplantation Chimera

Associated Chemicals: Interleukin-1beta (0) ; Myd88 protein, mouse (0) ; Myeloid Differentiation Factor 88 (0) ; Myosin Heavy Chains (0) ; Receptors, Interleukin-1 Type I (0) ; enhanced green fluorescent protein (0) ; Green Fluorescent Proteins (147336-22-9) ; Freund's Adjuvant (9007-81-2)

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