Redox signals that regulate the vascular response to injury.

Multiple enzymes may stimulate ROS production in VSMC and endothelial cells. These include NADH/NADPH oxidase, xanthine oxidase, lipoxygenases, cyclooxygenase, P-450 monooxygenases, and the enzymes of mitochondrial oxidative phosphorylation. In addition to generation of intracellular O2- by these enzymes, extracellular stimuli including lipophilic substrates, membrane permeant oxidants (e.g., H2O2), cytokines, and growth factors may modulate cellular redox state. Both intracellular and extracellular ROS act as second-messengers to activate tyrosine and serine-threonine kinases, such as the MAP kinase family. As discussed in the previous sections, regulation of the MAP kinases is one example of the complexity of ROS-dependent signal transduction. Although the complexity of ROS-mediated signal transduction is daunting, the diversity offers multiple therapeutic targets for pharmacologic intervention.