Figure 2.
Effects of Nox4 in cardiovascular systems. Hydrogen peroxide generated by Nox4 appears to have many beneficial effects: it modulates basal expression of Nrf2, and promotes vascular tone by increasing membrane hyperpolarization and activation of eNOS. The activation of eNOS has other beneficial effects on vascular homeostasis that are anti-atherogenic and pro-angiogenic. Nox4-dependent hydrogen peroxide is also thought to preserve endothelial and cardiac function by promoting Hif1α stabilization to initiate pro-angiogenic and metabolic reprogramming. Furthermore, oxidants produced by Nox4 contribute to cell signaling, and differentiation. It is not entirely clear why oxidants generated by Nox4 are protective rather than harmful; however, its excess expression has been associated with dysfunction under some circumstances.