The role of hydrogen peroxide in endothelial proliferative responses

Hydrogen peroxide (H2O2) is a recently recognized second messenger regulating proliferation in mammalian cells. Endothelial cells possess NADPH oxidases, which produce the H202 precursor superoxide (.O2-) in response to receptor-mediated signaling. Multiple physiologic agents have been shown to stimulate endothelial cells to produce .O2-/H2O2, including growth factors, such as vascular endothelial growth factor and transforming growth factor-beta1, and alterations in biomechanical forces, such as shear stress and cyclic strain. Downstream effects of these stimuli can often be inhibited by scavenging H2O2. Low concentrations of H2O2 stimulate proliferation or enhanced survival in a wide variety of cell types. Also, low concentrations of H2O2 stimulate endothelial migration as well as tube formation in an in vitro model of angiogenesis. Although low concentrations of H2O2 have been shown to be involved in numerous signal transduction pathways and to independently stimulate mitogenesis, there has been little information presented on precisely how mammalian cells respond biochemically to these low concentrations of H2O2. Recently a functional proteomics approach has been utilized to identify proteins responsive to low concentrations of H2O2 in human endothelial cells.