Title:Novel Targets of Metformin in Cardioprotection: Beyond the Effects Mediated by AMPK
Volume: 27
Issue: 1
Author(s): Samir Bolívar*, Laura Noriega, Stefany Ortega, Estefanie Osorio, Wendy Rosales, Xilene Mendoza and Evelyn Mendoza-Torres*
Affiliation:
- Healthcare Pharmacy and Pharmacology Research Group, Facultad de Quimica y Farmacia, Universidad del Atlantico, Barranquilla,Colombia
- Advaced Research Group in Biomedicine, Universidad Libre Seccional Barranquilla,Colombia
Keywords:
Metformin, myocardial ischemia, cardiac remodeling, AMPK, heart failure, fibrosis.
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.
