Metformin Protects the Heart Against Hypertrophic and Apoptotic Remodeling After Myocardial Infarction
Cardiovascular complications are the most prevalent cause of morbidity and mortality in diabetic patients. Metformin is currently the first-line blood glucose-lowering agent with potential relevance to cardiovascular diseases. However, the underpinning mechanisms of action remain elusive. Here, we r...
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doaj-f55650f42f154aba962b6f520cc766202020-11-24T21:17:00ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122019-02-011010.3389/fphar.2019.00154441530Metformin Protects the Heart Against Hypertrophic and Apoptotic Remodeling After Myocardial InfarctionHalyna Loi0Frederic Boal1Frederic Boal2Helene Tronchere3Helene Tronchere4Mathieu Cinato5Mathieu Cinato6Solomiia Kramar7Oleksandra Oleshchuk8Mykhaylo Korda9Oksana Kunduzova10Oksana Kunduzova11Department of Pharmacology, I. Horbachevsky Ternopil State Medical University, Ternopil, UkraineNational Institute of Health and Medical Research (INSERM) U1048, Institute of Cardiovascular and Metabolic Diseases, Toulouse, FranceUMR1048, Paul Sabatier University, Toulouse, FranceNational Institute of Health and Medical Research (INSERM) U1048, Institute of Cardiovascular and Metabolic Diseases, Toulouse, FranceUMR1048, Paul Sabatier University, Toulouse, FranceNational Institute of Health and Medical Research (INSERM) U1048, Institute of Cardiovascular and Metabolic Diseases, Toulouse, FranceUMR1048, Paul Sabatier University, Toulouse, FranceDepartment of Pharmacology, I. Horbachevsky Ternopil State Medical University, Ternopil, UkraineDepartment of Pharmacology, I. Horbachevsky Ternopil State Medical University, Ternopil, UkraineDepartment of Pharmacology, I. Horbachevsky Ternopil State Medical University, Ternopil, UkraineNational Institute of Health and Medical Research (INSERM) U1048, Institute of Cardiovascular and Metabolic Diseases, Toulouse, FranceUMR1048, Paul Sabatier University, Toulouse, FranceCardiovascular complications are the most prevalent cause of morbidity and mortality in diabetic patients. Metformin is currently the first-line blood glucose-lowering agent with potential relevance to cardiovascular diseases. However, the underpinning mechanisms of action remain elusive. Here, we report that metformin represses cardiac apoptosis at least in part through inhibition of Forkhead box O1 (FoxO1) pathway. In a mouse model of ischemia-reperfusion (I/R), treatment with metformin attenuated cardiac and hypertrophic remodeling after 14 days of post-reperfusion. Additionally, cardiac expression of brain-like natriuretic peptide (BNP) was significantly reduced in metformin-treated mice after 14 days of cardiac I/R. In cultured H9C2 cells, metformin counteracted hypertrophic and apoptotic responses to metabolic or hypoxic stress. FoxO1 silencing by siRNA abolished anti-apoptotic effect of metformin under hypoxic stress in H9C2 cells. Taken together, these results suggest that metformin protects the heart against hypertrophic and apoptotic remodeling after myocardial infarction.https://www.frontiersin.org/article/10.3389/fphar.2019.00154/fullmetforminmyocardial infarctionhypertrophyapoptosiscardiac remodeling |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Halyna Loi Frederic Boal Frederic Boal Helene Tronchere Helene Tronchere Mathieu Cinato Mathieu Cinato Solomiia Kramar Oleksandra Oleshchuk Mykhaylo Korda Oksana Kunduzova Oksana Kunduzova |
spellingShingle |
Halyna Loi Frederic Boal Frederic Boal Helene Tronchere Helene Tronchere Mathieu Cinato Mathieu Cinato Solomiia Kramar Oleksandra Oleshchuk Mykhaylo Korda Oksana Kunduzova Oksana Kunduzova Metformin Protects the Heart Against Hypertrophic and Apoptotic Remodeling After Myocardial Infarction Frontiers in Pharmacology metformin myocardial infarction hypertrophy apoptosis cardiac remodeling |
author_facet |
Halyna Loi Frederic Boal Frederic Boal Helene Tronchere Helene Tronchere Mathieu Cinato Mathieu Cinato Solomiia Kramar Oleksandra Oleshchuk Mykhaylo Korda Oksana Kunduzova Oksana Kunduzova |
author_sort |
Halyna Loi |
title |
Metformin Protects the Heart Against Hypertrophic and Apoptotic Remodeling After Myocardial Infarction |
title_short |
Metformin Protects the Heart Against Hypertrophic and Apoptotic Remodeling After Myocardial Infarction |
title_full |
Metformin Protects the Heart Against Hypertrophic and Apoptotic Remodeling After Myocardial Infarction |
title_fullStr |
Metformin Protects the Heart Against Hypertrophic and Apoptotic Remodeling After Myocardial Infarction |
title_full_unstemmed |
Metformin Protects the Heart Against Hypertrophic and Apoptotic Remodeling After Myocardial Infarction |
title_sort |
metformin protects the heart against hypertrophic and apoptotic remodeling after myocardial infarction |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Pharmacology |
issn |
1663-9812 |
publishDate |
2019-02-01 |
description |
Cardiovascular complications are the most prevalent cause of morbidity and mortality in diabetic patients. Metformin is currently the first-line blood glucose-lowering agent with potential relevance to cardiovascular diseases. However, the underpinning mechanisms of action remain elusive. Here, we report that metformin represses cardiac apoptosis at least in part through inhibition of Forkhead box O1 (FoxO1) pathway. In a mouse model of ischemia-reperfusion (I/R), treatment with metformin attenuated cardiac and hypertrophic remodeling after 14 days of post-reperfusion. Additionally, cardiac expression of brain-like natriuretic peptide (BNP) was significantly reduced in metformin-treated mice after 14 days of cardiac I/R. In cultured H9C2 cells, metformin counteracted hypertrophic and apoptotic responses to metabolic or hypoxic stress. FoxO1 silencing by siRNA abolished anti-apoptotic effect of metformin under hypoxic stress in H9C2 cells. Taken together, these results suggest that metformin protects the heart against hypertrophic and apoptotic remodeling after myocardial infarction. |
topic |
metformin myocardial infarction hypertrophy apoptosis cardiac remodeling |
url |
https://www.frontiersin.org/article/10.3389/fphar.2019.00154/full |
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