Bueno-Beti, C;
Tafuni, A;
Chelko, SP;
Sheppard, MN;
Field, E;
Tollit, J;
Heenan, IK;
... Asimaki, A; + view all
(2023)
Innate immune signaling in hearts and buccal mucosa cells of patients with arrhythmogenic cardiomyopathy.
Heart Rhythm O2
, 4
(10)
pp. 650-659.
10.1016/j.hroo.2023.09.006.
(In press).
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Abstract
Background: Nuclear factor κB (NF-κB) signaling in cardiac myocytes causes disease in a mouse model of arrhythmogenic cardiomyopathy (ACM) by mobilizing CCR2-expressing macrophages that promote myocardial injury and arrhythmias. Buccal mucosa cells exhibit pathologic features similar to those seen in cardiac myocytes in patients with ACM. Objectives: We sought to determine if persistent innate immune signaling via NF-κB occurs in cardiac myocytes in patients with ACM and if this is associated with myocardial infiltration of proinflammatory cells expressing CCR2. We also determined if buccal mucosa cells from young subjects with inherited disease alleles exhibit NF-κB signaling. Methods: We analyzed myocardium from ACM 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 NF-κB signaling. We also counted myocardial CCR2-expressing cells. Results: RelA/p65 signal was seen in numerous cardiac myocyte nuclei in 34 of 36 cases of ACM but not in 19 age-matched control individuals. Cells expressing CCR2 were increased in patient hearts in numbers directly correlated with the number of cardiac myocytes showing NF-κB signaling. NF-κB signaling was observed in buccal cells in young subjects with active disease. Conclusions: Patients with clinically active ACM 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.
| Type: | Article |
|---|---|
| Title: | Innate immune signaling in hearts and buccal mucosa cells of patients with arrhythmogenic cardiomyopathy |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.hroo.2023.09.006 |
| Publisher version: | https://doi.org/10.1016/j.hroo.2023.09.006 |
| Language: | English |
| Additional information: | © 2023 Heart Rhythm Society. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-ncnd/4.0/). |
| Keywords: | Arrhythmogenic cardiomyopathy; Innate immune signaling; Nuclear factor kB; Proinflammatory macrophages; Buccal mucosa cells |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10179612 |
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