Figure 4.

Antioxidative mechanisms of statins. The core NAD(P)H oxidase comprises five components: p40^phox (PHOX for phagocyte oxidase), p47^phox, p67^phox, p22^phox, and gp91^phox. In the resting cell (left), three of these five components, p40^phox, p47^phox, and p67^phox,exist in the cytosol as a complex. The other two components, p22^phox and gp91^phox, are located in the membranes. When it is stimulated by angiotensin, the cytosolic component becomes heavily phosphorylated and the entire cytosolic complex migrates to the membrane. Activation requires the participation not only of the core subunits but also of two low-molecular-weight guanine nucleotide-binding proteins, Rac and Rap. During activation, Rac binds GTP and migrates to the membrane along with the core cytosolic complex. Treatment with statin down-regulates AT1-receptor expression and inhibits Rac1 GTPase, a necessary component of the NAD(P)H oxidase complex.