FIG. 3.

Nox activation in the cardiovascular system. Nox1, Nox2, Nox4, and Nox5 are members of the Nox family that are expressed in the cardiovascular system. Nox2 is the classical Nox that is primarily characterized in leukocytes and related to host defence responses. In order to be activated, cytosolic subunits (p47phox, p67phox, and Rac 1/2) should translocate from the cytosol to the membrane and bind to the other two membrane-bound subunits, Nox2 and p22phox. ROS is generated once the whole enzyme complex is formed. Nox1 activation is similar to Nox2, but it depends on the cytosolic subunits NoxO1 (a homologue of p47phox) and NoxA1 (a homologue of p67phox) in order to be active. Nox4 only depends on p22phox in order to be active, is constitutively activated, and ROS production is regulated by Poldip2. Nox5 does not depend on any other subunits to be activated. It has four EF hands, which are binding sites for calcium. Nox5 activity is regulated not only by calcium changes in the cells, but also by calmodulin and by phosphorylation of kinases.