The role of monoamine oxidases in Duchenne muscular dystrophy-associated cardiomyopathy

Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular degenerative disorder caused by mutations in the DMD gene coding for dystrophin. It is characterized by progressive muscle wasting and weakness affecting peripheral muscle, respiratory, and cardiac function. Presently, the leading cause of death in DMD is cardiomyopathy, occurring in the second decade of life. Therefore, it is critical to diagnose and manage DMD-associated cardiomyopathy to improve the life expectancy and quality of life in DMD patients. Currently, there is no agreed-upon standard of care for DMD-related cardiomyopathy. This is due to the poor understanding of the pathogenetic mechanisms involved, thus necessitating the identification of novel therapeutic targets. To this end, we investigated the mechanisms underlying dystrophic cardiomyopathy and aimed at identifying molecular players contributing to the disease development that could be targeted therapeutically. Specifically, we looked at the contribution of monoamine oxidases-generated reactive oxygen species. We saw that MAO activity is increased in the mdx heart, leading to increased oxidative stress, mitochondrial dysfunction, apoptosis, and cardiac dysfunction.