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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...

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Autores principales: Daud, Elias, Ertracht, Offir, Bandel, Nadav, Moady, Gassan, Shehadeh, Monah, Reuveni, Tali, Atar, Shaul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
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.
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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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