Reactive oxygen species as mediators of signal transduction in cardiovascular disease.

Reduction-oxidation (redox) reactions that generate reactive oxygen species (ROS) have been identified as important chemical processes that regulate signal transduction. Because increased ROS may be a risk factor for cardiovascular events such as unstable angina, myocardial infarction and sudden death, understanding the biological processes that generate ROS and the intracellular signals elicited by ROS will be important to gain insight into the pathogenesis of these diseases. In this review, we discuss the enzymes that generate ROS in cardiovascular tissues, the role of the mitogen-activated protein (MAP) kinase pathway in redox-sensitive signal transduction, and focus on tyrosine kinases as proximate "sensors" for redox-mediated signal events. The mechanisms by which these kinases regulate gene transcription are then discussed to provide insight into the pathogenic roles of ROS in hypertension, atherosclerosis and vascular remodeling.