ADENOSINE STIMULATES PROLIFERATION OF HUMAN ENDOTHELIAL-CELLS IN CULTURE

The effect of adenosine on proliferation of human endothelial cells was investigated by adding adenosine to the medium of cultures derived from human umbilical veins. Cell counts on cultures grown in 10 muM adenosine for 4-7 days were 41-53% greater than counts from control cultures. In contrast, 10 muM adenosine had no effect on growth of a human fibroblast cell strain (IMR-90). Neither inosine nor 2',5'-dideoxyadenosine influenced endothelial cell growth at concentrations of 0.1 or 10 muM. Addition of adenosine deaminase abolished the proliferative effect of added adenosine and inhibited proliferation by 16% in control cultures, suggesting that endogenous adenosine may enhance proliferation in culture. The adenosine receptor antagonist, 8-phenyltheophylline, at 0.1 and 1.0 muM blocked the enhanced proliferation caused by 10 muM adenosine. Addition of 10 muM adenosine enhanced DNA synthesis in endothelial cell cultures as indicated by an increased incorporation of [H-3]thymidine into acid-insoluble cell material. The results indicate that addition of physiological concentrations of adenosine to human umbilical vein endothelial cell cultures stimulates proliferation, possibly via a surface receptor, and suggest that adenosine may be a factor for human endothelial cell growth and possibly angiogenesis.