Therapeutic Strategies for Combating Reactive Oxygen Species in Cardiovascular Diseases

Reactive oxygen species (ROS) have a role in the pathogenesis of various cardiovascular diseases (CVDs), including atherosclerosis, ischemic-reperfusion injury, ischemic heart disease, vascular endothelial dysfunction, and heart failure. Oxidative stress is caused when the equilibrium between free radical generation and antioxidant capacity is disrupted. Unfortunately, numerous clinical trials conducted using different antioxidants failed to provide beneficial outcomes in the treatment or prevention of CVDs. It appears to be more effective to directly target ROS production to preserve cellular redox balance and mitigate oxidative stress. In this chapter, the pathophysiology of ROS-mediated CVDs, including apoptosis, ferroptosis, fibrosis, inflammation, and contractile dysfunction, are discussed. We also summarize potential sources of ROS, including NOX, XORs, MPO, COX, LOX, mitochondrial respiratory chain, and noncoupling NOS, along with addressing some of their inhibitors. Also, enzymatic antioxidants such as GPX4, SOD, CAT, Prx, and Trx and nonenzymatic antioxidants such as GSH and vitamins E and C are explained. In addition, potential ROS modulators are discussed in depth, including HIF, NRF-2, HSP, FOXO, and AMPK. Finally, we shed light on ferroptosis as a major source of ROS and different anti-ferroptotic agents in CVDs. Collectively, this chapter highlights therapeutic approaches for combating ROS production in different CVDs.