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The impact of empagliflozin on cardiac physiology and fibrosis early after myocardial infarction in non-diabetic rats
BACKGROUND: Myocardial fibrosis is a multistep process, which results in collagen deposition in the injured muscle. Empagliflozin, a sodium-glucose cotransporter 2 inhibitor (SGLT2i), decreases cardiovascular events risk. Little is known on the effects of empagliflozin in non-diabetic patients early...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254247/ https://www.ncbi.nlm.nih.gov/pubmed/34215277 http://dx.doi.org/10.1186/s12933-021-01322-6 |
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author | Daud, Elias Ertracht, Offir Bandel, Nadav Moady, Gassan Shehadeh, Monah Reuveni, Tali Atar, Shaul |
author_facet | Daud, Elias Ertracht, Offir Bandel, Nadav Moady, Gassan Shehadeh, Monah Reuveni, Tali Atar, Shaul |
author_sort | Daud, Elias |
collection | PubMed |
description | BACKGROUND: Myocardial fibrosis is a multistep process, which results in collagen deposition in the injured muscle. Empagliflozin, a sodium-glucose cotransporter 2 inhibitor (SGLT2i), decreases cardiovascular events risk. Little is known on the effects of empagliflozin in non-diabetic patients early post myocardial infarction. METHODS: Fourteen non-diabetic rats underwent myocardial infarction induction, and treated or not (control)immediately after myocardial infarction by daily empagliflozin (30 mg/kg/day). We evaluated cardiac function at baseline, 2 and 4 weeks after myocardial infarction by echocardiography, and prior to sacrifice by Millar pressure–volume system. We performed histological and biochemical evaluation of fibrosis and humoral factors promoting fibrosis. RESULTS: Baseline ejection fractions were 69.9 ± 5.3% and 76.4 ± 5.4%, and dropped to final values of 40.1 ± 5.8% and 39.4 ± 5.4% in the control and empagliflozin groups, respectively (P < 0.001 vs. baseline, P > 0.05 between groups). Collagen deposition, measured as collagen volume fraction, was higher in both the scar and the remote cardiac areas of the control group 79.1 ± 6.2% and 4.6 ± 2.5% for control, and 53.8 ± 5.4% and 2.5 ± 1.3% for empagliflozin group, respectively (P < 0.05 for each). Remote cardiac muscle collagen, measured by hydroxyproline, was 4.1 ± 0.4 μg/μl and 3.6 ± 0.2 μg/μl (P = 0.07). TGF-β1 and Smad3 expression decreased by empagliflozin—18.73 ± 16.32%, 9.16 ± 5.69% and 16.32 ± 5.4%, 7.00 ± 5.28% in the control and empagliflozin groups, respectively (P < 0.05). CONCLUSION/INTERPRETATION: Empagliflozin administered early after myocardial infarction reduce myocardial fibrosis and inhibit the TGF-β1/Smad3 fibrotic pathway, probably prior to exerting any hemodynamic or physiological effect. |
format | Online Article Text |
id | pubmed-8254247 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-82542472021-07-06 The impact of empagliflozin on cardiac physiology and fibrosis early after myocardial infarction in non-diabetic rats Daud, Elias Ertracht, Offir Bandel, Nadav Moady, Gassan Shehadeh, Monah Reuveni, Tali Atar, Shaul Cardiovasc Diabetol Original Investigation BACKGROUND: Myocardial fibrosis is a multistep process, which results in collagen deposition in the injured muscle. Empagliflozin, a sodium-glucose cotransporter 2 inhibitor (SGLT2i), decreases cardiovascular events risk. Little is known on the effects of empagliflozin in non-diabetic patients early post myocardial infarction. METHODS: Fourteen non-diabetic rats underwent myocardial infarction induction, and treated or not (control)immediately after myocardial infarction by daily empagliflozin (30 mg/kg/day). We evaluated cardiac function at baseline, 2 and 4 weeks after myocardial infarction by echocardiography, and prior to sacrifice by Millar pressure–volume system. We performed histological and biochemical evaluation of fibrosis and humoral factors promoting fibrosis. RESULTS: Baseline ejection fractions were 69.9 ± 5.3% and 76.4 ± 5.4%, and dropped to final values of 40.1 ± 5.8% and 39.4 ± 5.4% in the control and empagliflozin groups, respectively (P < 0.001 vs. baseline, P > 0.05 between groups). Collagen deposition, measured as collagen volume fraction, was higher in both the scar and the remote cardiac areas of the control group 79.1 ± 6.2% and 4.6 ± 2.5% for control, and 53.8 ± 5.4% and 2.5 ± 1.3% for empagliflozin group, respectively (P < 0.05 for each). Remote cardiac muscle collagen, measured by hydroxyproline, was 4.1 ± 0.4 μg/μl and 3.6 ± 0.2 μg/μl (P = 0.07). TGF-β1 and Smad3 expression decreased by empagliflozin—18.73 ± 16.32%, 9.16 ± 5.69% and 16.32 ± 5.4%, 7.00 ± 5.28% in the control and empagliflozin groups, respectively (P < 0.05). CONCLUSION/INTERPRETATION: Empagliflozin administered early after myocardial infarction reduce myocardial fibrosis and inhibit the TGF-β1/Smad3 fibrotic pathway, probably prior to exerting any hemodynamic or physiological effect. BioMed Central 2021-07-02 /pmc/articles/PMC8254247/ /pubmed/34215277 http://dx.doi.org/10.1186/s12933-021-01322-6 Text en © The Author(s) 2021 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 | Original Investigation Daud, Elias Ertracht, Offir Bandel, Nadav Moady, Gassan Shehadeh, Monah Reuveni, Tali Atar, Shaul The impact of empagliflozin on cardiac physiology and fibrosis early after myocardial infarction in non-diabetic rats |
title | The impact of empagliflozin on cardiac physiology and fibrosis early after myocardial infarction in non-diabetic rats |
title_full | The impact of empagliflozin on cardiac physiology and fibrosis early after myocardial infarction in non-diabetic rats |
title_fullStr | The impact of empagliflozin on cardiac physiology and fibrosis early after myocardial infarction in non-diabetic rats |
title_full_unstemmed | The impact of empagliflozin on cardiac physiology and fibrosis early after myocardial infarction in non-diabetic rats |
title_short | The impact of empagliflozin on cardiac physiology and fibrosis early after myocardial infarction in non-diabetic rats |
title_sort | impact of empagliflozin on cardiac physiology and fibrosis early after myocardial infarction in non-diabetic rats |
topic | Original Investigation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254247/ https://www.ncbi.nlm.nih.gov/pubmed/34215277 http://dx.doi.org/10.1186/s12933-021-01322-6 |
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