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DNA Damage, an Innocent Bystander in Atrial Fibrillation and Other Cardiovascular Diseases?
Atrial Fibrillation (AF) is the most common clinical tachyarrhythmia with a strong tendency to progress in time. AF is difficult to treat and therefore there is a great need to dissect root causes of AF with the ultimate goal to develop mechanism-based (drug) therapies. New findings related to mecha...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7198718/ https://www.ncbi.nlm.nih.gov/pubmed/32411727 http://dx.doi.org/10.3389/fcvm.2020.00067 |
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author | Ramos, Kennedy S. Brundel, Bianca J. J. M. |
author_facet | Ramos, Kennedy S. Brundel, Bianca J. J. M. |
author_sort | Ramos, Kennedy S. |
collection | PubMed |
description | Atrial Fibrillation (AF) is the most common clinical tachyarrhythmia with a strong tendency to progress in time. AF is difficult to treat and therefore there is a great need to dissect root causes of AF with the ultimate goal to develop mechanism-based (drug) therapies. New findings related to mechanisms driving AF progression indicate a prime role for DNA damage-induced metabolic remodeling. A recent study uncovered that AF results in oxidative DNA damage and consequently excessive poly-ADP-ribose polymerase 1 (PARP1) activation and nicotinamide adenine dinucleotide (NAD(+)) depletion and finally atrial cardiomyocyte electrical and contractile dysfunction. This newly elucidated role of DNA damage in AF opens opportunities for novel therapeutic strategies. Recently developed PARP inhibitors, such as ABT-888 and olaparib, provide beneficial effects in limiting experimental AF, and are also found to limit atherosclerotic coronary artery disease and heart failure. Another therapeutic option to protect against AF is to replenish the NAD(+) pool by supplementation with NAD(+) or its precursors, such as nicotinamide and nicotinamide riboside. In this review, we describe the role of DNA damage-mediated metabolic remodeling in AF and other cardiovascular diseases, discuss novel druggable targets for AF and highlight future directions for clinical trials with drugs directed at PARP1-NAD(+) pathway with the ultimate aim to preserve quality of life and to attenuate severe complications such as heart failure or stroke in patients with AF. |
format | Online Article Text |
id | pubmed-7198718 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-71987182020-05-14 DNA Damage, an Innocent Bystander in Atrial Fibrillation and Other Cardiovascular Diseases? Ramos, Kennedy S. Brundel, Bianca J. J. M. Front Cardiovasc Med Cardiovascular Medicine Atrial Fibrillation (AF) is the most common clinical tachyarrhythmia with a strong tendency to progress in time. AF is difficult to treat and therefore there is a great need to dissect root causes of AF with the ultimate goal to develop mechanism-based (drug) therapies. New findings related to mechanisms driving AF progression indicate a prime role for DNA damage-induced metabolic remodeling. A recent study uncovered that AF results in oxidative DNA damage and consequently excessive poly-ADP-ribose polymerase 1 (PARP1) activation and nicotinamide adenine dinucleotide (NAD(+)) depletion and finally atrial cardiomyocyte electrical and contractile dysfunction. This newly elucidated role of DNA damage in AF opens opportunities for novel therapeutic strategies. Recently developed PARP inhibitors, such as ABT-888 and olaparib, provide beneficial effects in limiting experimental AF, and are also found to limit atherosclerotic coronary artery disease and heart failure. Another therapeutic option to protect against AF is to replenish the NAD(+) pool by supplementation with NAD(+) or its precursors, such as nicotinamide and nicotinamide riboside. In this review, we describe the role of DNA damage-mediated metabolic remodeling in AF and other cardiovascular diseases, discuss novel druggable targets for AF and highlight future directions for clinical trials with drugs directed at PARP1-NAD(+) pathway with the ultimate aim to preserve quality of life and to attenuate severe complications such as heart failure or stroke in patients with AF. Frontiers Media S.A. 2020-04-28 /pmc/articles/PMC7198718/ /pubmed/32411727 http://dx.doi.org/10.3389/fcvm.2020.00067 Text en Copyright © 2020 Ramos and Brundel. http://creativecommons.org/licenses/by/4.0/ 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) and the copyright owner(s) 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 | Cardiovascular Medicine Ramos, Kennedy S. Brundel, Bianca J. J. M. DNA Damage, an Innocent Bystander in Atrial Fibrillation and Other Cardiovascular Diseases? |
title | DNA Damage, an Innocent Bystander in Atrial Fibrillation and Other Cardiovascular Diseases? |
title_full | DNA Damage, an Innocent Bystander in Atrial Fibrillation and Other Cardiovascular Diseases? |
title_fullStr | DNA Damage, an Innocent Bystander in Atrial Fibrillation and Other Cardiovascular Diseases? |
title_full_unstemmed | DNA Damage, an Innocent Bystander in Atrial Fibrillation and Other Cardiovascular Diseases? |
title_short | DNA Damage, an Innocent Bystander in Atrial Fibrillation and Other Cardiovascular Diseases? |
title_sort | dna damage, an innocent bystander in atrial fibrillation and other cardiovascular diseases? |
topic | Cardiovascular Medicine |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7198718/ https://www.ncbi.nlm.nih.gov/pubmed/32411727 http://dx.doi.org/10.3389/fcvm.2020.00067 |
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