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The Cardiac Mineralocorticoid Receptor (MR): A Therapeutic Target Against Ventricular Arrhythmias
Mineralocorticoid antagonists have been shown to be useful in the treatment of severe heart failure and may even save lives in this context. However, the reason for the beneficial action of these drugs, as well as the physiological role played by the cardiac mineralocorticoid receptor (MR), are stil...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274808/ https://www.ncbi.nlm.nih.gov/pubmed/34262530 http://dx.doi.org/10.3389/fendo.2021.694758 |
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author | Rossier, Michel F. |
author_facet | Rossier, Michel F. |
author_sort | Rossier, Michel F. |
collection | PubMed |
description | Mineralocorticoid antagonists have been shown to be useful in the treatment of severe heart failure and may even save lives in this context. However, the reason for the beneficial action of these drugs, as well as the physiological role played by the cardiac mineralocorticoid receptor (MR), are still poorly understood. While the proinflammatory action of aldosterone on the heart and the resulting fibrosis partly explain the improvement due to the anti-mineralocorticoid therapy, the reduction in sudden death is probably related to a lower occurrence of ventricular arrhythmias. In this review, the author explains the physiological mechanism linking the positive chronotropic response induced by aldosterone observed in vitro with isolated ventricular cardiomyocytes and the increased risk of ventricular arrhythmias reported in vivo in hyperaldosteronism. He describes the molecular steps involved between MR activation and acceleration of spontaneous myocyte contractions, including expression of a specific micro RNA (miR204), down-regulation of a silencing transcription factor (NRSF), and re-expression of a fetal gene encoding a low threshold voltage-gated calcium channel (CaV3.2). Finally, he provides evidence suggesting aldosterone-independent and redox-sensitive mechanisms of MR activation in cardiac myocytes. Taken together, this information suggests that the use of anti-mineralocorticoid therapy could benefit the heart by preventing ventricular arrhythmias, not only in established hyperaldosteronism, but also in various pathological situations such as Cushing’s disease, oxidative stress, or even diabetes mellitus. |
format | Online Article Text |
id | pubmed-8274808 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-82748082021-07-13 The Cardiac Mineralocorticoid Receptor (MR): A Therapeutic Target Against Ventricular Arrhythmias Rossier, Michel F. Front Endocrinol (Lausanne) Endocrinology Mineralocorticoid antagonists have been shown to be useful in the treatment of severe heart failure and may even save lives in this context. However, the reason for the beneficial action of these drugs, as well as the physiological role played by the cardiac mineralocorticoid receptor (MR), are still poorly understood. While the proinflammatory action of aldosterone on the heart and the resulting fibrosis partly explain the improvement due to the anti-mineralocorticoid therapy, the reduction in sudden death is probably related to a lower occurrence of ventricular arrhythmias. In this review, the author explains the physiological mechanism linking the positive chronotropic response induced by aldosterone observed in vitro with isolated ventricular cardiomyocytes and the increased risk of ventricular arrhythmias reported in vivo in hyperaldosteronism. He describes the molecular steps involved between MR activation and acceleration of spontaneous myocyte contractions, including expression of a specific micro RNA (miR204), down-regulation of a silencing transcription factor (NRSF), and re-expression of a fetal gene encoding a low threshold voltage-gated calcium channel (CaV3.2). Finally, he provides evidence suggesting aldosterone-independent and redox-sensitive mechanisms of MR activation in cardiac myocytes. Taken together, this information suggests that the use of anti-mineralocorticoid therapy could benefit the heart by preventing ventricular arrhythmias, not only in established hyperaldosteronism, but also in various pathological situations such as Cushing’s disease, oxidative stress, or even diabetes mellitus. Frontiers Media S.A. 2021-06-28 /pmc/articles/PMC8274808/ /pubmed/34262530 http://dx.doi.org/10.3389/fendo.2021.694758 Text en Copyright © 2021 Rossier https://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 | Endocrinology Rossier, Michel F. The Cardiac Mineralocorticoid Receptor (MR): A Therapeutic Target Against Ventricular Arrhythmias |
title | The Cardiac Mineralocorticoid Receptor (MR): A Therapeutic Target Against Ventricular Arrhythmias |
title_full | The Cardiac Mineralocorticoid Receptor (MR): A Therapeutic Target Against Ventricular Arrhythmias |
title_fullStr | The Cardiac Mineralocorticoid Receptor (MR): A Therapeutic Target Against Ventricular Arrhythmias |
title_full_unstemmed | The Cardiac Mineralocorticoid Receptor (MR): A Therapeutic Target Against Ventricular Arrhythmias |
title_short | The Cardiac Mineralocorticoid Receptor (MR): A Therapeutic Target Against Ventricular Arrhythmias |
title_sort | cardiac mineralocorticoid receptor (mr): a therapeutic target against ventricular arrhythmias |
topic | Endocrinology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274808/ https://www.ncbi.nlm.nih.gov/pubmed/34262530 http://dx.doi.org/10.3389/fendo.2021.694758 |
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