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Inherited cardiomyopathies caused by troponin mutations

Genetic investigations of cardiomyopathy in the recent two decades have revealed a large number of mutations in the genes encoding sarcomeric proteins as a cause of inherited hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), or restrictive cardiomyopathy (RCM). Most functional analyse...

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Autores principales: Lu, Qun-Wei, Wu, Xiao-Yan, Morimoto, Sachio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Science Press 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3627712/
https://www.ncbi.nlm.nih.gov/pubmed/23610579
http://dx.doi.org/10.3969/j.issn.1671-5411.2013.01.014
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author Lu, Qun-Wei
Wu, Xiao-Yan
Morimoto, Sachio
author_facet Lu, Qun-Wei
Wu, Xiao-Yan
Morimoto, Sachio
author_sort Lu, Qun-Wei
collection PubMed
description Genetic investigations of cardiomyopathy in the recent two decades have revealed a large number of mutations in the genes encoding sarcomeric proteins as a cause of inherited hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), or restrictive cardiomyopathy (RCM). Most functional analyses of the effects of mutations on cardiac muscle contraction have revealed significant changes in the Ca(2+)-regulatory mechanism, in which cardiac troponin (cTn) plays important structural and functional roles as a key regulatory protein. Over a hundred mutations have been identified in all three subunits of cTn, i.e., cardiac troponins T, I, and C. Recent studies on cTn mutations have provided plenty of evidence that HCM- and RCM-linked mutations increase cardiac myofilament Ca(2+) sensitivity, while DCM-linked mutations decrease it. This review focuses on the functional consequences of mutations found in cTn in terms of cardiac myofilament Ca(2+) sensitivity, ATPase activity, force generation, and cardiac troponin I phosphorylation, to understand potential molecular and cellular pathogenic mechanisms of the three types of inherited cardiomyopathy.
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spelling pubmed-36277122013-04-22 Inherited cardiomyopathies caused by troponin mutations Lu, Qun-Wei Wu, Xiao-Yan Morimoto, Sachio J Geriatr Cardiol Review Genetic investigations of cardiomyopathy in the recent two decades have revealed a large number of mutations in the genes encoding sarcomeric proteins as a cause of inherited hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), or restrictive cardiomyopathy (RCM). Most functional analyses of the effects of mutations on cardiac muscle contraction have revealed significant changes in the Ca(2+)-regulatory mechanism, in which cardiac troponin (cTn) plays important structural and functional roles as a key regulatory protein. Over a hundred mutations have been identified in all three subunits of cTn, i.e., cardiac troponins T, I, and C. Recent studies on cTn mutations have provided plenty of evidence that HCM- and RCM-linked mutations increase cardiac myofilament Ca(2+) sensitivity, while DCM-linked mutations decrease it. This review focuses on the functional consequences of mutations found in cTn in terms of cardiac myofilament Ca(2+) sensitivity, ATPase activity, force generation, and cardiac troponin I phosphorylation, to understand potential molecular and cellular pathogenic mechanisms of the three types of inherited cardiomyopathy. Science Press 2013-03 /pmc/articles/PMC3627712/ /pubmed/23610579 http://dx.doi.org/10.3969/j.issn.1671-5411.2013.01.014 Text en Institute of Geriatric Cardiology http://creativecommons.org/licenses/by-nc-sa/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License, which allows readers to alter, transform, or build upon the article and then distribute the resulting work under the same or similar license to this one. The work must be attributed back to the original author and commercial use is not permitted without specific permission.
spellingShingle Review
Lu, Qun-Wei
Wu, Xiao-Yan
Morimoto, Sachio
Inherited cardiomyopathies caused by troponin mutations
title Inherited cardiomyopathies caused by troponin mutations
title_full Inherited cardiomyopathies caused by troponin mutations
title_fullStr Inherited cardiomyopathies caused by troponin mutations
title_full_unstemmed Inherited cardiomyopathies caused by troponin mutations
title_short Inherited cardiomyopathies caused by troponin mutations
title_sort inherited cardiomyopathies caused by troponin mutations
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3627712/
https://www.ncbi.nlm.nih.gov/pubmed/23610579
http://dx.doi.org/10.3969/j.issn.1671-5411.2013.01.014
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