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Pathogenesis of arrhythmogenic cardiomyopathy: role of inflammation

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Abstract

Arrhythmogenic cardiomyopathy (AC) is an inherited disease characterized by progressive breakdown of heart muscle, myocardial tissue death, and fibrofatty replacement. In most cases of AC, the primary lesion occurs in one of the genes encoding desmosomal proteins, disruption of which increases membrane fragility at the intercalated disc. Disrupted, exposed desmosomal proteins also serve as epitopes that can trigger an autoimmune reaction. Damage to cell membranes and autoimmunity provoke myocardial inflammation, a key feature in early stages of the disease. In several preclinical models, targeting inflammation has been shown to blunt disease progression, but translation to the clinic has been sparse. Here we review current understanding of inflammatory pathways and how they interact with injured tissue and the immune system in AC. We further discuss the potential role of immunomodulatory therapies in AC.

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Acknowledgements

We thank Lisa Trahan for editorial assistance.

Funding

Y.N.L was supported by China Medical University (CMU107-N-05). General lab support was provided by grants from the National Institutes of Health (R01 HL124074, R01 HL135866 and R01 HL147570), the Peer-Reviewed Medical Research Program of the U.S. Department of Defense (PR150620), and the Cedars-Sinai Board of Governors. EM holds the Mark S. Siegel Family Foundation Distinguished Chair of the Cedars-Sinai Medical Center.

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  1. Cedars-Sinai Medical Center, Smidt Heart Institute, 127 S. San Vicente Blvd., Los Angeles, CA, 90048, USA

    Yen-Nien Lin, Ahmed Ibrahim, Eduardo Marbán & Eugenio Cingolani

  2. Division of Cardiovascular Medicine, Department of Medicine, China Medical University and Hospital, Taichung, Taiwan

    Yen-Nien Lin

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  1. Yen-Nien Lin
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  2. Ahmed Ibrahim
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Correspondence to Eugenio Cingolani.

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E.M. owns founder’s equity in Capricor Therapeutics.

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Lin, YN., Ibrahim, A., Marbán, E. et al. Pathogenesis of arrhythmogenic cardiomyopathy: role of inflammation. Basic Res Cardiol 116, 39 (2021). https://doi.org/10.1007/s00395-021-00877-5

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