This review discusses recent findings that have challenged the long-held dogma in the field that reduction in reaction oxygen species (ROS) would improve clinical outcome in the patients with cardiovascular disease (CVD). Attempts will be made to shed light on the differential spatial and temporal roles of subcellular ROS in vascular endothelium in health and disease. Recent findings demonstrating that above-physiological levels of endothelial cell (EC)-specific NADPH oxidase-derived ROS in vivo exert beneficial effects on vascular endothelium will be discussed. The paradoxical roles of ROS in CVD suggest that subcellular sources and types of ROS may play crucial roles in the prevention, development, and progression of CVD. A better understanding of the precise mechanisms by which subcellular ROS modulate cardiovascular health and functions will certainly better prepare us with effective treatment modalities for CVD.
Part of the book: Free Radicals and Diseases
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 Here, we will discuss published and unpublished work that has helped elucidate the molecular mechanisms by which subcellular ROS levels, duration and localization modulate metabolic pathways, including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