Angiotensin II and Oxidative Stress in the Failing Heart

Significance: Despite recent medical advances, cardiovascular disease and heart failure (HF) continue to be major health concerns, and related mortality remains high. As a result, investigation of the mechanisms involved in the development of HF continues to be an active field of study. Recent Advances: The renin-angiotensin system (RAS) and its effector molecule, angiotensin (Ang) II, affect cardiac function through both systemic and local actions, and have been shown to play a major role in cardiac remodeling and dysfunction in the failing heart. Many of the downstream effects of AngII signaling are mediated by elevated levels of reactive oxygen species (ROS) and oxidative stress, which have also been implicated in the pathology of HF. Critical Issues: Inhibitors of the RAS have proven beneficial in the treatment of patients at risk for and suffering from HF, but remain only partially effective. ROS can be generated from several different sources, and the oxidative state is normally tightly regulated in the heart. How AngII increases ROS levels and causes dysregulation of the cardiac oxidative state has been the subject of considerable interest in recent years. Future Directions: A better understanding of this process and the mechanisms involved should lead to the development of more effective HF therapies and improved outcomes. Antioxid. Redox Signal. 19, 1095-1109.