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Novel Targets of Metformin in Cardioprotection: Beyond the Effects Mediated by AMPK

Author(s):

Samir Bolívar*, Laura Noriega, Stefany Ortega, Estefanie Osorio, Wendy Rosales, Xilene Mendoza and Evelyn Mendoza-Torres   Pages 1 - 11 ( 11 )

Abstract:


Ischemic heart disease is the main cause of death globally. In the heart, the ischemia/reperfusion injury gives rise to a complex cascade of molecular signals, called cardiac remodeling, which generates harmful consequences for the contractile function of the myocardium and consequently heart failure. Metformin is the drug of choice in the treatment of type 2 diabetes mellitus. Clinical data suggest the direct effects of this drug on cardiac metabolism and studies in animal models showed that metformin activates the classical pathway of AMP-activated protein kinase (AMPK), generating cardioprotective effects during cardiac remodeling, hypertrophy and fibrosis. Furthermore, new studies have emerged about other targets of metformin with a potential role in cardioprotection. This state of the art review, shows the available scientific evidence of the cardioprotective potential of metformin and its possible effects beyond AMPK. Targeting of autophagy, mitochondrial function and miRNAs are also explored as cardioprotective approaches along with a therapeutic potential. Further advances related to the biological effects of metformin and cardioprotective approaches may provide new therapies to protect the heart and prevent cardiac remodeling and heart failure.

Keywords:

Metformin, myocardial ischemia, cardiac remodeling, AMPK, heart failure, fibrosis.

Affiliation:

Faculty of Chemistry and Pharmacy, Universidad del Atlántico, Barranquilla, Faculty of Chemistry and Pharmacy, Universidad del Atlántico, Barranquilla, Faculty of Chemistry and Pharmacy, Universidad del Atlántico, Barranquilla, Advaced Research Group in Biomedicine, Universidad Libre Seccional Barranquilla, Advaced Research Group in Biomedicine, Universidad Libre Seccional Barranquilla, Universidad Metropolitana, Grupo de Investigación en Medicina Traslacional (GIMET), Barranquilla, Advaced Research Group in Biomedicine, Universidad Libre Seccional Barranquilla



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