Regulation of Transcription Factors by Reactive Oxygen Species and Nitric Oxide in Vascular Physiology and Pathology

Significance: Cardiovascular diseases are the main cause of death worldwide and pose an immense economical burden. In most cases, the underlying problem is vascular occlusion by atherosclerotic plaques. Importantly, different cell types of the vascular wall and the immune system play crucial roles in atherosclerosis at different stages of the disease. Furthermore, atherosclerosis and conditions recognized as risk factors are characterized by a reduced availability of the vasoprotective molecule nitric oxide and an increase in reactive oxygen species, so-called oxidative stress. Transcription factors function as intracellular signal integrators and relays and thus, play a central role in cellular responses to changing conditions. Recent Advances: Work on specific transcriptional regulators has uncovered many of their functions and the upstream pathways modulating their activity in response to reactive oxygen and nitrogen species. Here, we have reviewed for a few selected examples how this can contribute not only to protection against atherosclerosis development but also to disease progression and the occurrence of clinical manifestations, such as plaque rupture. Critical Issues: Transcription factors have pleiotropic outputs and often also divergent functions in different cell types and tissues. Thus, in light of potential severe adverse side effects, a global activation or inhibition of particular transcriptions factors does not seem a feasible therapeutic option. Future Directions: A further in-depth characterization of the cell-and stage-specific actions and regulation of transcription factors in atherosclerosis with respect to protein-protein interactions and target genes could open up new avenues for prevention or therapeutic interventions in this vascular disease.