Nrf2 Transcription Factor and Heme Oxygenase-1 as Modulators of Vascular Injury and Angiogenesis

The cytoprotective actions of Nrf2 transcription factor against vascular injuries associated with oxidative stress and tissue ischemia are widely reported. Amongst Nrf2 target genes, heme oxygenase-1 (HO-1) is responsible for at least a part of such protective effects by playing strong antioxidant and anti-inflammatory roles in the vascular system. Nonetheless, the area of Nrf2/HO-1 functioning could be extended to the control of vessel growth. Although the angiogenic involvement of HO-1 in physiological states and under conditions of tissue damage is well demonstrated, a direct role of Nrf2 in the process of blood vessel formation is just coming to light. Nrf2 has been linked to known angiogenic signaling pathways, comprising not only HO-1, but also vascular endothelial growth factor and hypoxia-inducible factor-1, and suggested to act in normal vascular development as well as in the formation of blood vessels nourishing tumor. Strikingly, Nrf2 deficiency may promote oxidative stress-related inflammatory neovascularization accompanying damaged/ischemic tissue regeneration. Thus, further studies are definitely required for a thorough assessment of Nrf2 place in the processes of blood vessel formation.