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Sodium-Glucose Cotransporter 2 Inhibitors and Heart Failure: A Bedside-to-Bench Journey
Type 2 diabetes mellitus (T2DM) and heart failure (HF) are multifactorial diseases sharing common risk factors, such as obesity, hyperinsulinemia, and inflammation, with underlying mechanisms including endothelial dysfunction, inflammation, oxidative stress, and metabolic alterations. Cardiovascular...
Autores principales: | , , , , , , , , |
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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/PMC8733295/ https://www.ncbi.nlm.nih.gov/pubmed/35004918 http://dx.doi.org/10.3389/fcvm.2021.810791 |
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author | Cappetta, Donato De Angelis, Antonella Bellocchio, Gabriella Telesca, Marialucia Cianflone, Eleonora Torella, Daniele Rossi, Francesco Urbanek, Konrad Berrino, Liberato |
author_facet | Cappetta, Donato De Angelis, Antonella Bellocchio, Gabriella Telesca, Marialucia Cianflone, Eleonora Torella, Daniele Rossi, Francesco Urbanek, Konrad Berrino, Liberato |
author_sort | Cappetta, Donato |
collection | PubMed |
description | Type 2 diabetes mellitus (T2DM) and heart failure (HF) are multifactorial diseases sharing common risk factors, such as obesity, hyperinsulinemia, and inflammation, with underlying mechanisms including endothelial dysfunction, inflammation, oxidative stress, and metabolic alterations. Cardiovascular benefits of sodium-glucose cotransporter 2 (SGLT2) inhibitors observed in diabetic and non-diabetic patients are also related to their cardiac-specific, SGLT-independent mechanisms, in addition to the metabolic and hemodynamic effects. In search of the possible underlying mechanisms, a research campaign has been launched proposing varied mechanisms of action that include intracellular ion homeostasis, autophagy, cell death, and inflammatory processes. Moreover, the research focus was widened toward cellular targets other than cardiomyocytes. At the moment, intracellular sodium level reduction is the most explored mechanism of direct cardiac effects of SGLT2 inhibitors that mediate the benefits in heart failure in addition to glucose excretion and diuresis. The restoration of cardiac Na(+) levels with consequent positive effects on Ca(2+) handling can directly translate into improved contractility and relaxation of cardiomyocytes and have antiarrhythmic effects. In this review, we summarize clinical trials, studies on human cells, and animal models, that provide a vast array of data in support of repurposing this class of antidiabetic drugs. |
format | Online Article Text |
id | pubmed-8733295 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-87332952022-01-07 Sodium-Glucose Cotransporter 2 Inhibitors and Heart Failure: A Bedside-to-Bench Journey Cappetta, Donato De Angelis, Antonella Bellocchio, Gabriella Telesca, Marialucia Cianflone, Eleonora Torella, Daniele Rossi, Francesco Urbanek, Konrad Berrino, Liberato Front Cardiovasc Med Cardiovascular Medicine Type 2 diabetes mellitus (T2DM) and heart failure (HF) are multifactorial diseases sharing common risk factors, such as obesity, hyperinsulinemia, and inflammation, with underlying mechanisms including endothelial dysfunction, inflammation, oxidative stress, and metabolic alterations. Cardiovascular benefits of sodium-glucose cotransporter 2 (SGLT2) inhibitors observed in diabetic and non-diabetic patients are also related to their cardiac-specific, SGLT-independent mechanisms, in addition to the metabolic and hemodynamic effects. In search of the possible underlying mechanisms, a research campaign has been launched proposing varied mechanisms of action that include intracellular ion homeostasis, autophagy, cell death, and inflammatory processes. Moreover, the research focus was widened toward cellular targets other than cardiomyocytes. At the moment, intracellular sodium level reduction is the most explored mechanism of direct cardiac effects of SGLT2 inhibitors that mediate the benefits in heart failure in addition to glucose excretion and diuresis. The restoration of cardiac Na(+) levels with consequent positive effects on Ca(2+) handling can directly translate into improved contractility and relaxation of cardiomyocytes and have antiarrhythmic effects. In this review, we summarize clinical trials, studies on human cells, and animal models, that provide a vast array of data in support of repurposing this class of antidiabetic drugs. Frontiers Media S.A. 2021-12-23 /pmc/articles/PMC8733295/ /pubmed/35004918 http://dx.doi.org/10.3389/fcvm.2021.810791 Text en Copyright © 2021 Cappetta, De Angelis, Bellocchio, Telesca, Cianflone, Torella, Rossi, Urbanek and Berrino. 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 | Cardiovascular Medicine Cappetta, Donato De Angelis, Antonella Bellocchio, Gabriella Telesca, Marialucia Cianflone, Eleonora Torella, Daniele Rossi, Francesco Urbanek, Konrad Berrino, Liberato Sodium-Glucose Cotransporter 2 Inhibitors and Heart Failure: A Bedside-to-Bench Journey |
title | Sodium-Glucose Cotransporter 2 Inhibitors and Heart Failure: A Bedside-to-Bench Journey |
title_full | Sodium-Glucose Cotransporter 2 Inhibitors and Heart Failure: A Bedside-to-Bench Journey |
title_fullStr | Sodium-Glucose Cotransporter 2 Inhibitors and Heart Failure: A Bedside-to-Bench Journey |
title_full_unstemmed | Sodium-Glucose Cotransporter 2 Inhibitors and Heart Failure: A Bedside-to-Bench Journey |
title_short | Sodium-Glucose Cotransporter 2 Inhibitors and Heart Failure: A Bedside-to-Bench Journey |
title_sort | sodium-glucose cotransporter 2 inhibitors and heart failure: a bedside-to-bench journey |
topic | Cardiovascular Medicine |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8733295/ https://www.ncbi.nlm.nih.gov/pubmed/35004918 http://dx.doi.org/10.3389/fcvm.2021.810791 |
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