Thin filament cardiomyopathies: A review of genetics, disease mechanisms, and emerging therapeutics.

Autor:	Keyt LK; Department of Internal Medicine, University of California, San Diego, San Diego, CA, United States., Duran JM; Department of Cardiology, University of California, San Diego, San Diego, CA, United States., Bui QM; Department of Cardiology, University of California, San Diego, San Diego, CA, United States., Chen C; Department of Cardiology, University of California, San Diego, San Diego, CA, United States., Miyamoto MI; Providence Health, Mission Viejo, CA, United States., Silva Enciso J; Department of Cardiology, University of California, San Diego, San Diego, CA, United States., Tardiff JC; Department of Medicine and Biomedical Engineering, University of Arizona, Tucson, AZ, United States., Adler ED; Department of Cardiology, University of California, San Diego, San Diego, CA, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in cardiovascular medicine [Front Cardiovasc Med] 2022 Sep 07; Vol. 9, pp. 972301. Date of Electronic Publication: 2022 Sep 07 (Print Publication: 2022).
DOI:	10.3389/fcvm.2022.972301
Abstrakt:	All muscle contraction occurs due to the cyclical interaction between sarcomeric thin and thick filament proteins within the myocyte. The thin filament consists of the proteins actin, tropomyosin, Troponin C, Troponin I, and Troponin T. Mutations in these proteins can result in various forms of cardiomyopathy, including hypertrophic, restrictive, and dilated phenotypes and account for as many as 30% of all cases of inherited cardiomyopathy. There is significant evidence that thin filament mutations contribute to dysregulation of Ca 2+ within the sarcomere and may have a distinct pathomechanism of disease from cardiomyopathy associated with thick filament mutations. A number of distinct clinical findings appear to be correlated with thin-filament mutations: greater degrees of restrictive cardiomyopathy and relatively less left ventricular (LV) hypertrophy and LV outflow tract obstruction than that seen with thick filament mutations, increased morbidity associated with heart failure, increased arrhythmia burden and potentially higher mortality. Most therapies that improve outcomes in heart failure blunt the neurohormonal pathways involved in cardiac remodeling, while most therapies for hypertrophic cardiomyopathy involve use of negative inotropes to reduce LV hypertrophy or septal reduction therapies to reduce LV outflow tract obstruction. None of these therapies directly address the underlying sarcomeric dysfunction associated with thin-filament mutations. With mounting evidence that thin filament cardiomyopathies occur through a distinct mechanism, there is need for therapies targeting the unique, underlying mechanisms tailored for each patient depending on a given mutation. Competing Interests: JD reports personal fees from Lexeo during the conduct of the review. EA reports personal fees from Abiomed, Novartis, Abbott, non-financial support from Astra Zeneca, personal fees from Ionis Pharmaceuticals, Sana Biotechnology, Medtronic, other from Rocket Pharmaceuticals, Papillon Therapeutics, ResQ Pharmaceuticals, personal fees from Lexeo Pharmaceuticals, Cytokinetics, Endotronics, and during the conduct of the review. MM was employed by Providence Health. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Keyt, Duran, Bui, Chen, Miyamoto, Silva Enciso, Tardiff and Adler.)
Databáze:	MEDLINE
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