The Enigmatic Vascular NOX: From Artifact to Double Agent of Change

Abstract

NOXs (NADPH oxidases) comprise a family of proteins whose primary function is the production of reactive oxygen species, namely, superoxide anion and hydrogen peroxide. The prototype first being discovered and characterized in neutrophils, multiple NOXs are now known to be broadly expressed in cell and organ systems and whose phylogeny spans countless life forms beginning with prokaryotes. This long-enduring evolutionary conservation underscores the importance of fundamental NOX functions. This review chronicles a personal perspective of the field beginning with the discovery of NOXs in the vasculature and the advances achieved through the years as to our understanding of their mechanisms of action and role in oxidative stress and disease. Furthermore, applications of isoform-selective inhibitors to dissect the role of NOX isozymes in vascular biology, focusing on inflammation, pulmonary hypertension, and aging are described.