THE ANTIDIABETIC DRUGS AND MAO-RELATED OXIDATIVE STRESS: MAKE NEW FRIENDS BUT KEEP THE OLD

The global burden of cardiometabolic pathologies is expected to increase in the near future with most of related cardiovascular deaths occurring in low and middle-income countries. The major pathomechanisms that underlie these pathologies are chronic oxidative stress and low-grade inflammation, which promote each other in a vicious circle leading to both disease progression and the occurrence of complications. Heart failure, the end-stage of cardiometabolic diseases, is regarded as a ”systemic mitochondrial cytopathy” since mitochondria are the major sites of reactive oxygen species (ROS) generation. Monoamine oxidase (MAO) with two isoforms, MAO-A and MAO-B, located at the outer mitochondrial membrane, has emerged in the recent years as a constant enzymatic source of deleterious ROS in the diseased cardiovascular system whose expression and/or activity is increasing with the age. Moreover, inflammation is responsible for age-independent increase in MAO expression. A large body of research demonstrated the role of antidiabetics in improving the outcome of non-diabetic and diabetic patients with cardiovascular diseases yet the underlying pathomechanisms remain elusive. Metformin, the central pillar of therapy in type 2 diabetes, is the ”good old drug” with incompletely understood pleiotropic effects, including the antioxidant, which are responsible for the cardiovascular protection and anti-ageing properties. The sodium-glucose-cotransporter 2 inhibitors (SGLT-2i) are novel antidiabetic drugs which exert cardiovascular protection in the absence of diabetes via partially elucidated off-target effects. Here we provide evidence that MAO is a novel target of both classic and new antidiabetics in the human cardiovascular system.