Metformin Protects the Heart Against Hypertrophic and Apoptotic Remodeling After Myocardial Infarction.
apoptosis
cardiac remodeling
hypertrophy
metformin
myocardial infarction
Journal
Frontiers in pharmacology
ISSN: 1663-9812
Titre abrégé: Front Pharmacol
Pays: Switzerland
ID NLM: 101548923
Informations de publication
Date de publication:
2019
2019
Historique:
received:
07
12
2018
accepted:
08
02
2019
entrez:
16
3
2019
pubmed:
16
3
2019
medline:
16
3
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 30873028
doi: 10.3389/fphar.2019.00154
pmc: PMC6400884
doi:
Types de publication
Journal Article
Langues
eng
Pagination
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