Cargando…

Identifying potential functional impact of mutations and polymorphisms: linking heart failure, increased risk of arrhythmias and sudden cardiac death

Researchers and clinicians have discovered several important concepts regarding the mechanisms responsible for increased risk of arrhythmias, heart failure, and sudden cardiac death. One major step in defining the molecular basis of normal and abnormal cardiac electrical behavior has been the identi...

Descripción completa

Detalles Bibliográficos
Autores principales: Jagu, Benoît, Charpentier, Flavien, Toumaniantz, Gilles
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3778269/
https://www.ncbi.nlm.nih.gov/pubmed/24065925
http://dx.doi.org/10.3389/fphys.2013.00254
_version_ 1782285083690926080
author Jagu, Benoît
Charpentier, Flavien
Toumaniantz, Gilles
author_facet Jagu, Benoît
Charpentier, Flavien
Toumaniantz, Gilles
author_sort Jagu, Benoît
collection PubMed
description Researchers and clinicians have discovered several important concepts regarding the mechanisms responsible for increased risk of arrhythmias, heart failure, and sudden cardiac death. One major step in defining the molecular basis of normal and abnormal cardiac electrical behavior has been the identification of single mutations that greatly increase the risk for arrhythmias and sudden cardiac death by changing channel-gating characteristics. Indeed, mutations in several genes encoding ion channels, such as SCN5A, which encodes the major cardiac Na(+) channel, have emerged as the basis for a variety of inherited cardiac arrhythmias such as long QT syndrome, Brugada syndrome, progressive cardiac conduction disorder, sinus node dysfunction, or sudden infant death syndrome. In addition, genes encoding ion channel accessory proteins, like anchoring or chaperone proteins, which modify the expression, the regulation of endocytosis, and the degradation of ion channel a-subunits have also been reported as susceptibility genes for arrhythmic syndromes. The regulation of ion channel protein expression also depends on a fine-tuned balance among different other mechanisms, such as gene transcription, RNA processing, post-transcriptional control of gene expression by miRNA, protein synthesis, assembly and post-translational modification and trafficking. The aim of this review is to inventory, through the description of few representative examples, the role of these different biogenic mechanisms in arrhythmogenesis, HF and SCD in order to help the researcher to identify all the processes that could lead to arrhythmias. Identification of novel targets for drug intervention should result from further understanding of these fundamental mechanisms.
format Online
Article
Text
id pubmed-3778269
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-37782692013-09-24 Identifying potential functional impact of mutations and polymorphisms: linking heart failure, increased risk of arrhythmias and sudden cardiac death Jagu, Benoît Charpentier, Flavien Toumaniantz, Gilles Front Physiol Physiology Researchers and clinicians have discovered several important concepts regarding the mechanisms responsible for increased risk of arrhythmias, heart failure, and sudden cardiac death. One major step in defining the molecular basis of normal and abnormal cardiac electrical behavior has been the identification of single mutations that greatly increase the risk for arrhythmias and sudden cardiac death by changing channel-gating characteristics. Indeed, mutations in several genes encoding ion channels, such as SCN5A, which encodes the major cardiac Na(+) channel, have emerged as the basis for a variety of inherited cardiac arrhythmias such as long QT syndrome, Brugada syndrome, progressive cardiac conduction disorder, sinus node dysfunction, or sudden infant death syndrome. In addition, genes encoding ion channel accessory proteins, like anchoring or chaperone proteins, which modify the expression, the regulation of endocytosis, and the degradation of ion channel a-subunits have also been reported as susceptibility genes for arrhythmic syndromes. The regulation of ion channel protein expression also depends on a fine-tuned balance among different other mechanisms, such as gene transcription, RNA processing, post-transcriptional control of gene expression by miRNA, protein synthesis, assembly and post-translational modification and trafficking. The aim of this review is to inventory, through the description of few representative examples, the role of these different biogenic mechanisms in arrhythmogenesis, HF and SCD in order to help the researcher to identify all the processes that could lead to arrhythmias. Identification of novel targets for drug intervention should result from further understanding of these fundamental mechanisms. Frontiers Media S.A. 2013-09-20 /pmc/articles/PMC3778269/ /pubmed/24065925 http://dx.doi.org/10.3389/fphys.2013.00254 Text en Copyright © 2013 Jagu, Charpentier and Toumaniantz. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Jagu, Benoît
Charpentier, Flavien
Toumaniantz, Gilles
Identifying potential functional impact of mutations and polymorphisms: linking heart failure, increased risk of arrhythmias and sudden cardiac death
title Identifying potential functional impact of mutations and polymorphisms: linking heart failure, increased risk of arrhythmias and sudden cardiac death
title_full Identifying potential functional impact of mutations and polymorphisms: linking heart failure, increased risk of arrhythmias and sudden cardiac death
title_fullStr Identifying potential functional impact of mutations and polymorphisms: linking heart failure, increased risk of arrhythmias and sudden cardiac death
title_full_unstemmed Identifying potential functional impact of mutations and polymorphisms: linking heart failure, increased risk of arrhythmias and sudden cardiac death
title_short Identifying potential functional impact of mutations and polymorphisms: linking heart failure, increased risk of arrhythmias and sudden cardiac death
title_sort identifying potential functional impact of mutations and polymorphisms: linking heart failure, increased risk of arrhythmias and sudden cardiac death
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3778269/
https://www.ncbi.nlm.nih.gov/pubmed/24065925
http://dx.doi.org/10.3389/fphys.2013.00254
work_keys_str_mv AT jagubenoit identifyingpotentialfunctionalimpactofmutationsandpolymorphismslinkingheartfailureincreasedriskofarrhythmiasandsuddencardiacdeath
AT charpentierflavien identifyingpotentialfunctionalimpactofmutationsandpolymorphismslinkingheartfailureincreasedriskofarrhythmiasandsuddencardiacdeath
AT toumaniantzgilles identifyingpotentialfunctionalimpactofmutationsandpolymorphismslinkingheartfailureincreasedriskofarrhythmiasandsuddencardiacdeath