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.
Curr Pharm Des. 2021;27(1):80-90. doi: 10.2174/1381612826666200509232610.
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.
缺血性心脏病是全球主要的死亡原因。在心脏中，缺血/再灌注损伤引发了称为心脏重构的复杂分子信号级联反应，这对心肌的收缩功能产生有害影响，进而导致心力衰竭。二甲双胍是治疗 2 型糖尿病的首选药物。临床数据表明，该药物对心脏代谢有直接影响，动物模型研究表明，二甲双胍激活了 AMP 激活的蛋白激酶（AMPK）的经典途径，在心脏重构、肥大和纤维化过程中产生心脏保护作用。此外，关于二甲双胍的其他靶点在心脏保护中的潜在作用的新研究也已经出现。本综述介绍了二甲双胍的心脏保护潜力的现有科学证据，以及其在 AMPK 之外的可能作用。自噬、线粒体功能和 miRNA 也被探索为心脏保护方法，具有治疗潜力。与二甲双胍的生物学作用和心脏保护方法相关的进一步进展可能为保护心脏、预防心脏重构和心力衰竭提供新的治疗方法。
