Figure 1.

NOX2 and NOX4 are the major isoforms present in the cardiomyocyte. They are activated by a variety of stimuli (e.g. cytokines, mechanical stretch, growth factors, nutrient deprivation, metabolites) and G-protein coupled receptor agonists such as angiotensin II (Ang II) and endothelin-1 (ET-1). Their intracellular locations are also distinct, with NOX2 being located at the sarcolemma and NOX4 located in intracellular membrane compartments (ER/mitochondria/MAM). Another distinction between isoforms is the ROS produced. NOX2 generates superoxide (O₂^.-) but NOX4 generates predominantly hydrogen peroxide (H₂O₂). It is likely that the differing intracellular locations and ROS-generating properties underlie their functional differences. PDGF, platelet-derived growth factor; VEGF, vascular endothelial growth factor; EGF, epidermal growth factor; oxLDL, oxidized LDL.