Functional implications of Reactive Oxygen Species (ROS) in human blood vessels

Reactive oxygen species (ROS) play a significant role in the pathogenesis of human vascular disorders associated with endothelial dysfunction, such as atherosclerosis, hypertension, coronary artery disease, and diabetic vascular disease. Moreover, recent data show that ROS are also relevant in venous diseases such as venous insufficiency or varicose vein disease (Guzik et al. 2011). In general, the functional role of ROS in human vasculature is consistent with the majority of findings in animal models and cell culture, with main differences being related to the complexity of the system. This complexity is related not only to the concomitant expression of numerous oxidases (including Nox5) in human vessels in vivo but primarily to complicated regulation by many coinciding factors. While this is the case for every translational approach, for studies of reactive oxygen species, the task becomes particularly difficult. Furthermore, vascular pathologies in humans are much more dynamic and progress through more complex stages than observed in animal models. In humans, the sources and functional importance of ROS appear to differ at various stages of atherosclerotic plaque development. However, a number of solid studies have been performed on relatively large populations of subjects, and there is clear evidence as to the functional role of ROS in human vasculature and their regulation, which will be briefly discussed here. Similar to animal models, ROS are generated by all layers of the vascular wall, the endothelium, vascular smooth muscle cells (VSMCs) in the media, fibroblasts, and incoming inflammatory cells in the adventitia (Berry et al. 2000). In these compartments, ROS may have divergent sources and roles, although its effects on endothelial function and vascular nitric oxide bioavailability appear to be particularly important in relation to human vascular disease