AMP-activated protein kinase: A remarkable contributor to preserve a healthy heart against ROS injury

Heart failure is one of the leading causes of death and disability worldwide. Left ventricle remodeling, fibrosis, and ischemia/reperfusion injury all contribute to the deterioration of cardiac function and predispose to the onset of heart failure. Adenosine monophosphate-activated protein kinase (AMPK) is the universally recognized energy sensor which responds to low ATP levels and restores cellular metabolism. AMPK activation controls numerous cellular processes and, in the heart, it plays a pivotal role in preventing onset and progression of disease. Excessive reactive oxygen species (ROS) generation, known as oxidative stress, can activate AMPK, conferring an additional role of AMPK as a redox-sensor. In this review, we discuss recent insights into the crosstalk between ROS and AMPK. We describe the molecular mechanisms by which ROS activate AMPK and how AMPK signaling can further prevent heart failure progression. Ultimately, we review the potential therapeutic approaches to target AMPK for the treatment of cardiovascular disease and prevention of heart failure. [Display omitted] •Excessive reactive oxygen species generation can activate AMPK, conferring an additional role to AMPK as a redox sensor.•AMPK activation reduces oxidative stress by acting on Nox, mitochondria and antioxidant enzyme expression.•AMPK plays a crucial role in controlling oxidative stress in ischemia-reperfusion, cardiac hypertrophy or atherosclerosis.•By limiting ROS, AMPK protects the heart from failure and can prevent both HFpEF and HFrEF.