Macrophage mitochondrial superoxides as a target for atherosclerotic disease treatment.

ABSTRACT

Cardiovascular diseases (CVD) are the leading cause of death worldwide. Although many effective therapies exist, a substantial portion of patients remain unprotected by current measures. Recent advances in the understanding of the underpinning cause of CVD, atherosclerosis, have demonstrated the important causative role of inflammation in disease progression. Monocytes are important protagonists of atherosclerosis, and they have been shown to have elevated reliance on mitochondrial metabolism producing elevated levels of superoxides as a noxious byproduct. There exists a key link between mitochondrial superoxides production and inflammatory output in monocytes in the context of atherosclerosis. In this review we describe mitochondrial superoxide lowering strategies in order to broaden the scope of treatment strategies for CVD. We further explore strategies for more effective and selective targeting of the involved monocytes and macrophages in order to increase potency of effect and diminish side effects.