Selective targeting of NADPH oxidase for cardiovascular protection

The NADPH oxidase is a ubiquitously distributed multisubunit enzyme which generates superoxide from molecular oxygen using NADPH as the electron donor. In cardiovascular cells the main catalytic unit consists of two subunits, p22(phox) and one of five Nox isoforms, of which Nox1, Nox2 and Nox4 are the main isoforms expressed in cardiovascular cells. Nox1 and Nox2 require the association with cytosolic subunits for activity, whereas Nox4 appears to be constitutively active. Not only does the expression profile of these isoforms differ between different cell types, but individual isoforms appear to have distinct and separate locations within the cell. Nox enzymes have been linked to a range of cardiovascular pathologies including cardiac and vascular hypertrophy and fibrosis, atherosclerosis, vascular inflammation and angiogenesis, in addition to cellular proliferation and differentiation. Moreover, it is becoming increasingly clear that the individual Nox isoforms have delineated roles within the cell and are linked with specific downstream effects. This review will highlight some of the most important recent studies and discuss how specifically targeting the subunits of the NADPH oxidase complex may have therapeutic potential.