For decades, elevated levels of reactive oxygen species (ROS) have been associated with the pathogenesis of cardiovascular diseases (CVD), including myocardial ischemia and infarction (MI). However, several large clinical trials failed to demonstrate beneficial outcomes in response to the global reduction of ROS in patients with underlying CVD. Recent studies from our and other labs showed that it is rather a critical balance between mitochondrial and cytosolic ROS than total ROS levels which determines resilience of coronary endothelial cells (EC). Here, we will discuss published and unpublished work that has helped elucidate the molecular mechanisms by which subcellular ROS levels, duration and localization modulate metabolic pathways, including glycolysis and oxidative phosphorylation, energy production and utilization, and dNTP synthesis in EC. These redox-regulated processes play critical roles in providing resilience to EC which in turn help protect existing coronary vessels and induce coronary angiogenesis to improve post-MI recovery of cardiac function.
Part of the book: Oxidoreductase