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Direct cardiac effects of SGLT2 inhibitors
Sodium-glucose-cotransporter 2 inhibitors (SGLT2is) demonstrate large cardiovascular benefit in both diabetic and non-diabetic, acute and chronic heart failure patients. These inhibitors have on-target (SGLT2 inhibition in the kidney) and off-target effects that likely both contribute to the reporte...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8933888/ https://www.ncbi.nlm.nih.gov/pubmed/35303888 http://dx.doi.org/10.1186/s12933-022-01480-1 |
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author | Chen, Sha Coronel, Ruben Hollmann, Markus W. Weber, Nina C. Zuurbier, Coert J. |
author_facet | Chen, Sha Coronel, Ruben Hollmann, Markus W. Weber, Nina C. Zuurbier, Coert J. |
author_sort | Chen, Sha |
collection | PubMed |
description | Sodium-glucose-cotransporter 2 inhibitors (SGLT2is) demonstrate large cardiovascular benefit in both diabetic and non-diabetic, acute and chronic heart failure patients. These inhibitors have on-target (SGLT2 inhibition in the kidney) and off-target effects that likely both contribute to the reported cardiovascular benefit. Here we review the literature on direct effects of SGLT2is on various cardiac cells and derive at an unifying working hypothesis. SGLT2is acutely and directly (1) inhibit cardiac sodium transporters and alter ion homeostasis, (2) reduce inflammation and oxidative stress, (3) influence metabolism, and (4) improve cardiac function. We postulate that cardiac benefit modulated by SGLT2i’s can be commonly attributed to their inhibition of sodium-loaders in the plasma membrane (NHE-1, Nav1.5, SGLT) affecting intracellular sodium-homeostasis (the sodium-interactome), thereby providing a unifying view on the various effects reported in separate studies. The SGLT2is effects are most apparent when cells or hearts are subjected to pathological conditions (reactive oxygen species, inflammation, acidosis, hypoxia, high saturated fatty acids, hypertension, hyperglycemia, and heart failure sympathetic stimulation) that are known to prime these plasmalemmal sodium-loaders. In conclusion, the cardiac sodium-interactome provides a unifying testable working hypothesis and a possible, at least partly, explanation to the clinical benefits of SGLT2is observed in the diseased patient. |
format | Online Article Text |
id | pubmed-8933888 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-89338882022-03-23 Direct cardiac effects of SGLT2 inhibitors Chen, Sha Coronel, Ruben Hollmann, Markus W. Weber, Nina C. Zuurbier, Coert J. Cardiovasc Diabetol Review Sodium-glucose-cotransporter 2 inhibitors (SGLT2is) demonstrate large cardiovascular benefit in both diabetic and non-diabetic, acute and chronic heart failure patients. These inhibitors have on-target (SGLT2 inhibition in the kidney) and off-target effects that likely both contribute to the reported cardiovascular benefit. Here we review the literature on direct effects of SGLT2is on various cardiac cells and derive at an unifying working hypothesis. SGLT2is acutely and directly (1) inhibit cardiac sodium transporters and alter ion homeostasis, (2) reduce inflammation and oxidative stress, (3) influence metabolism, and (4) improve cardiac function. We postulate that cardiac benefit modulated by SGLT2i’s can be commonly attributed to their inhibition of sodium-loaders in the plasma membrane (NHE-1, Nav1.5, SGLT) affecting intracellular sodium-homeostasis (the sodium-interactome), thereby providing a unifying view on the various effects reported in separate studies. The SGLT2is effects are most apparent when cells or hearts are subjected to pathological conditions (reactive oxygen species, inflammation, acidosis, hypoxia, high saturated fatty acids, hypertension, hyperglycemia, and heart failure sympathetic stimulation) that are known to prime these plasmalemmal sodium-loaders. In conclusion, the cardiac sodium-interactome provides a unifying testable working hypothesis and a possible, at least partly, explanation to the clinical benefits of SGLT2is observed in the diseased patient. BioMed Central 2022-03-18 /pmc/articles/PMC8933888/ /pubmed/35303888 http://dx.doi.org/10.1186/s12933-022-01480-1 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Review Chen, Sha Coronel, Ruben Hollmann, Markus W. Weber, Nina C. Zuurbier, Coert J. Direct cardiac effects of SGLT2 inhibitors |
title | Direct cardiac effects of SGLT2 inhibitors |
title_full | Direct cardiac effects of SGLT2 inhibitors |
title_fullStr | Direct cardiac effects of SGLT2 inhibitors |
title_full_unstemmed | Direct cardiac effects of SGLT2 inhibitors |
title_short | Direct cardiac effects of SGLT2 inhibitors |
title_sort | direct cardiac effects of sglt2 inhibitors |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8933888/ https://www.ncbi.nlm.nih.gov/pubmed/35303888 http://dx.doi.org/10.1186/s12933-022-01480-1 |
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