SERUM-ALBUMIN IS A SPECIFIC INHIBITOR OF APOPTOSIS IN HUMAN ENDOTHELIAL-CELLS

Excess blood vessels are removed by apoptosis of endothelial cells, ho wever, the signals responsible for this have not been defined, Apoptos is of cultured human umbilical vein endothelial cells is induced by de privation of serum or adhesion, In this paper, apoptosis in human umbi lical vein and microvascular endothelium was induced by deprivation of serum and or adhesion, Apoptosis was confirmed on the basis of morpho logy, ultrastructure and internucleosomal cleavage of DNA, Loss of end othelial adhesion was found to be an early event in cultured endotheli al cell apoptosis and was exploited to quantitate apoptosis. The effec t of: bovine serum albumin; human serum albumin; recombinant human alb umin; dithiothreitol reduced human and bovine albumin; CNBr treated hu man and bovine albumin as well as ovalbumin upon endothelial apoptosis was determined, Native bovine and human albumin as well as recombinan t human material inhibited apoptosis at physiological concentrations w ith identical dose response curves in both umbilical vein and microvas cular cells, Dithiothreitol treatment destroyed all protective activit y while bovine but not human albumin was partially inactivated by CNBr treatment, The unrelated protein ovalbumin was not protective, Albumi n did not inhibit apoptosis if cells were also deprived of adhesion, T he data suggest that albumin is a specific inhibitor of human endothel ial apoptosis but does not protect cells also deprived of adhesion, Re duced supply of albumin to endothelium in poorly perfused blood vessel s may provide a mechanism for the removal of excess blood vessels in r emodelling tissues. Also, the failure of albumin to protect endothelia l cells deprived of adhesion from apoptosis may reflect the need to re move potentially micro-embolic cells detached due to trauma.