Key result
MyD88 knockout prevented the development of cardiac fibrosis, ventricular dilation, and impaired heart function in a mouse model of inflammatory dilated cardiomyopathy.
Why the study?
Does MyD88/IL-1 signaling control cardiac fibrosis and heart failure progression in a mouse model of inflammatory dilated cardiomyopathy?
Does MyD88/IL-1 signaling control cardiac fibrosis and heart failure progression in a mouse model of inflammatory dilated cardiomyopathy?
MyD88/IL-1 signaling in bone marrow-derived cells is critical for the development of postinflammatory cardiac fibrosis and progression to heart failure in a mouse model.
MyD88/IL-1 signaling drives post-myocarditis fibrosis in mice; leaves open whether pathway inhibition benefits human heart failure.
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.
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Błyszczuk et al. (2009) studied Inflammatory dilated cardiomyopathy. MyD88 knockout vs. Wild-type mice was evaluated on Cardiac fibrosis, ventricular dilation, and impaired heart function. MyD88 knockout prevented the development of cardiac fibrosis, ventricular dilation, and impaired heart function in a mouse model of inflammatory dilated cardiomyopathy.
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