LAUSR

A large body of evidence indicates that mitochondrial dysfunction has a major role in the pathogenesis of multiple cardiovascular disorders. Over the past 2 decades, extraordinary efforts have been focused on the development of agents that specifically target mitochondria for the treatment of cardiovascular disease. Despite such an intensive wave of investigation, no drugs specifically conceived to modulate mitochondrial functions are currently available for the clinical management of cardiovascular disease. In this Review, we discuss the therapeutic potential of targeting mitochondria in patients with cardiovascular disease, examine the obstacles that have restrained the development of mitochondria-targeting agents thus far, and identify strategies that might empower the full clinical potential of this approach.Mitochondrial dysfunction has a major role in the pathogenesis of multiple cardiovascular disorders. In this Review, Galluzzi and colleagues discuss the therapeutic potential of mitochondria-targeting agents in the treatment of cardiovascular disease, examine the obstacles that have limited their development thus far, and identify strategies for the development of these promising therapeutic tools.Key pointsMitochondrial dysfunction is involved in the pathogenesis of multiple cardiovascular disorders, including myocardial infarction, cardiomyopathies of various aetiologies, arrhythmias, hypertension, and atherosclerosis.Mitochondria are essential for the physiological activity of the cardiovascular system owing to their crucial role in bioenergetic and anabolic metabolism and their central position in intracellular Ca2+ fluxes.In addition to losing their physiological functions, damaged mitochondria actively drive inflammatory responses and waves of regulated cell death that contribute to the pathogenesis of cardiovascular disease.An intensive wave of investigation attempted to develop mitochondria-targeting agents for preventing or treating cardiovascular disorders in patients, with rather dismal results.Molecules with improved pharmacological features, precise mechanistic insights into mitochondrial processes, and reconsidering the pathogenesis of some cardiovascular disorders are instrumental for the development of mitochondria-targeting agents with clinical use.