The role of NADPH oxidase in vascular disease--hypertension, atherosclerosis & stroke.

The family of NADPH oxidase (Nox) proteins plays an integral role in the homeostatic functions of the cell, including gene expression, cell migration, proliferation, senescence and inflammation. There are currently 4 isoforms (Nox1, 2, 4 and 5) that are expressed across all cell types of the vascular system and play an important role in many physiological processes such as endothelial function, vascular tone and angiogenesis. The balance between Nox derived reactive oxygen species production and their elimination by dismutase enzymes is a critical finely tuned process. It is when this balance is shifted in disease states, either leading to an over- or under-production of reactive oxygen species that vascular injury develops. To date, Nox isoforms have been linked to the development of many vascular diseases including hypertension, atherosclerosis and stroke. The contribution of each isoform to the pathophysiology of vascular disease appears to be a matter of debate with most studies suggesting that Nox1 oxidase and Nox2 oxidase play deleterious roles, whereas Nox4 oxidase potentially plays a protective role in the vasculature. This review will discuss the current knowledge on the role of Nox derived oxidative stress in the pathophysiology of various vascular diseases including hypertension and atherosclerosis.