Oxidative stress as a regulator of gene expression in the vasculature

Oxidative stress and the production of intracellular reactive oxygen specie s (ROS) have been implicated in the pathogenesis of a variety of diseases. In excess, ROS and their byproducts that are capable of causing oxidative d amage may be cytotoxic to cells. However, it is now well established that m oderate amounts of ROS play a role in signal transduction processes such as cell growth and posttranslational modification of proteins. Oxidants, anti oxidants, and other determinants of the intracellular reduction-oxidation ( redox) state play an important role in the regulation of gene expression. R ecent insights into the etiology and pathogenesis of atherosclerosis sugges t that this disease may be viewed as an inflammatory disease linked to an a bnormality 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 gen e expression mediated via specific redox-sensitive signal transduction path ways 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 pathogene sis of atherosclerosis and other inflammatory diseases but also for the dev elopment of novel therapeutic treatment strategies.