Redox control of tissue factor expression in smooth muscle cells and other vascular cells

Reactive oxygen species (ROS) have been demonstrated as novel signaling molecules in a variety of cell types. It has become clear that many cells, including vascular cells, are able to generate ROS at a basal level and in an inducible manner. Increased ROS production has been related to various diseases. Thus, the understanding of ROS-generating enzymes and the modulation of gene expression by redox-sensitive signaling pathways have gained increasing interest. Several enzymes, in addition to mitochondria, can produce ROS, including isoforms of the NADPH oxidase, a superoxide-generating enzyme originally identified in phagocytes. Many growth factors and cytokines, as well as physicochemical stress, stimulate ROS production and subsequently activate redox-sensitive signaling pathways. A role for ROS in the control of coagulation has been suggested, and the key activator of the extrinsic coagulation cascade, tissue factor (TF), has been shown to be modulated by ROS in several cell types, including vascular cells. This chapter presents some evidence for redox-sensitive signaling cascades involved in the regulation of TF in smooth muscle cells and other vascular cells.