Decreased cultured endothelial cell proliferation in high glucose medium is reversed by antioxidants: new insights on the pathophysiological mechanisms of diabetic vascular complications.

Exposure to hyperglycemia slows the rate of proliferation of cultured human endothelial cells. Recently, it has been reported that glucose may autoxidize generating free radicals which have been hypothesized to delay cell replication time. To test whether oxidative stress has an effect on delaying cell replication time in hyperglycemic conditions, human endothelial cells cultured from umbilical veins were incubated in 5 or 20 mM glucose, either alone or in the presence of one of three different antioxidants: superoxide dismutase (SOD), catalase and glutathione (GSH). Cells grown in medium with 5 mM glucose, with or without antioxidants, yielded similar population doubling times and cell cycle phase distributions. Significantly lower growth parameters were observed in cells grown in medium with 20 mM glucose, without antioxidants. The presence of the antioxidant reverted them to almost normal growth. These data show that high glucose levels may delay endothelial cells replication time through the generation of free radicals, suggesting a possible pathophysiological linkage between the high levels of glucose and the development of microvascular complications of diabetes, possibly suggesting a new therapeutic approach to prevent such complications.