Oxidative damage of endothelial cells

This study sought to investigate the consequences of different degrees of oxidative stress on endothelial cells, using a cultured endothelial cell model; principally bovine aortic endothelial cells, subjected to oxidative stress.;High concentrations of H2O2 or a superoxide generating system caused rapid endothelial cell death, as evidenced by increased membrane permeability, which could be partially protected by myoglobin.;Extracellular H2O2 caused a rapid increase in intracellular peroxidation but was also eliminated by endothelial cells. However, the anti-oxidant capacity of the bovine endothelial cells was very weak and could be overcome by as little as 5 femtomol hydrogen peroxide per cell. The effects were directly related to the amount of H2O2 available to each cell, rather than the concentration.;Exposure to relatively low amounts of H2O2 (<0.5 picomol/cell) led to reduced endothelial cell function including prostacyclin production and mitochondrial dehydrogenase activity, and inhibited cell migration and proliferation. The cells showed gradual, partial recovery from these damaging effects.;At low amounts (0.1 to 0.5 picomol/cell) H2O2 induced endothelial cell apoptosis within 48 hours of the exposure. After this time, some of the surviving cells showed evidence of senescence(definition) and could remain in culture for up to 30 days. Senescence was accompanied by an increase in cytoplasmic volume and accumulation of lipofusion. Investigation of -galactosidase activity suggested that the increased enzyme expression was linked to cell cycle rather than senescence.;In conclusion, endothelial cells are very sensitive to oxidative damage but the nature of the damage is related to the degree of oxidative stress. The effects of oxidative stress may play an important role in atherosclerotic and cardiovascular diseases.