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- W4386858521 abstract "BackgroundNFκB signaling in cardiac myocytes causes disease in a mouse model of arrhythmogenic cardiomyopathy by mobilizing CCR2-expressing macrophages which promote myocardial injury and arrhythmias. Buccal mucosa cells exhibit pathologic features similar to those seen in cardiac myocytes in patients with arrhythmogenic cardiomyopathy.ObjectivesWe sought to determine if persistent innate immune signaling via NFκB occurs in cardiac myocytes in patients with arrhythmogenic cardiomyopathy and if this is associated with myocardial infiltration of pro-inflammatory cells expressing CCR2. We also determined if buccal mucosa cells from young subjects with inherited disease alleles exhibit NFκB signaling.MethodsWe analyzed myocardium from arrhythmogenic cardiomyopathy patients who died suddenly or required cardiac transplantation. We also analyzed buccal mucosa cells from young subjects with inherited disease alleles. The presence of immunoreactive signal for RelA/p65 in nuclei of cardiac myocytes and buccal cells was used as a reliable indicator of active NFκB signaling. We also counted myocardial CCR2-expressing cells.ResultsRelA/p65 signal was seen in numerous cardiac myocyte nuclei in 34 of 36 cases of arrhythmogenic cardiomyopathy but not in 19 age-matched controls. Cells expressing CCR2 were increased in patient hearts in numbers directly correlated with the number of cardiac myocytes showing NFκB signaling. NFκB signaling was observed in buccal cells in young subjects with active disease.ConclusionsPatients with clinically active arrhythmogenic cardiomyopathy exhibit persistent innate immune responses in cardiac myocytes and buccal mucosa cells reflecting a local and systemic inflammatory process. Such individuals may benefit from anti-inflammatory therapy." @default.
- W4386858521 created "2023-09-20" @default.
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- W4386858521 date "2023-09-01" @default.
- W4386858521 modified "2023-10-16" @default.
- W4386858521 title "Innate Immune Signaling in Hearts and Buccal Mucosa Cells of Patients with Arrhythmogenic Cardiomyopathy" @default.
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- W4386858521 doi "https://doi.org/10.1016/j.hroo.2023.09.006" @default.
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