title: Oxidative stress as a regulator of gene expression in the vasculature.
abstract: Oxidative stress and the production of intracellular reactive oxygen species (ROS) have been implicated in the pathogenesis of a variety of diseases. In excess, ROS and their byproducts that are capable of causing oxidative damage may be cytotoxic to cells. However, it is now well established that moderate amounts of ROS play a role in signal transduction processes such as cell growth and posttranslational modification of proteins. Oxidants, antioxidants, and other determinants of the intracellular reduction-oxidation (redox) state play an important role in the regulation of gene expression. Recent insights into the etiology and pathogenesis of atherosclerosis suggest that this disease may be viewed as an inflammatory disease linked to an abnormality in oxidation-mediated signals in the vasculature. In this review, we summarize the evidence supporting the notion that oxidative stress and the production of ROS function as physiological regulators of vascular gene expression mediated via specific redox-sensitive signal transduction pathways and transcriptional regulatory networks. Elucidating, at the molecular level, the regulatory processes involved in redox-sensitive vascular gene expression represents a foundation not only for understanding the pathogenesis of atherosclerosis and other inflammatory diseases but also for the development of novel therapeutic treatment strategies.
authors.affiliation: AtheroGenics, Inc, Alpharetta, GA 30004, USA.
authors.forename: C
authors.initials: C
authors.lastname: Kunsch
authors.forename: R M
authors.initials: RM
authors.lastname: Medford
mesh_terms: D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology; D001808:Blood Vessels / Q000473:pathology / Q000502:physiology* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology; D005786:Gene Expression Regulation; D006801:Humans; D018384:Oxidative Stress / Q000235:genetics*; D012307:Risk Factors; D015398:Signal Transduction