Serum albumin is a specific inhibitor of apoptosis in human endothelial cells.
Excess blood vessels are removed by apoptosis of endothelial cells, however, the signals responsible for this have not been defined. Apoptosis of cultured human umbilical vein endothelial cells is induced by deprivation of serum or adhesion. In this paper, apoptosis in human umbilical vein and microvascular endothelium was induced by deprivation of serum and or adhesion. Apoptosis was confirmed on the basis of morphology, ultrastructure and internucleosomal cleavage of DNA. Loss of endothelial adhesion was found to be an early event in cultured endothelial cell apoptosis and was exploited to quantitate apoptosis. The effect of: bovine serum albumin; human serum albumin; recombinant human albumin; dithiothreitol reduced human and bovine albumin; CNBr treated human and bovine albumin as well as ovalbumin upon endothelial apoptosis was determined. Native bovine and human albumin as well as recombinant human material inhibited apoptosis at physiological concentrations with identical dose response curves in both umbilical vein and microvascular cells. Dithiothreitol treatment destroyed all protective activity while bovine but not human albumin was partially inactivated by CNBr treatment. The unrelated protein ovalbumin was not protective. Albumin did not inhibit apoptosis if cells were also deprived of adhesion. The data suggest that albumin is a specific inhibitor of human endothelial apoptosis but does not protect cells also deprived of adhesion. Reduced supply of albumin to endothelium in poorly perfused blood vessels may provide a mechanism for the removal of excess blood vessels in remodelling tissues. Also, the failure of albumin to protect endothelial cells deprived of adhesion from apoptosis may reflect the need to remove potentially micro-embolic cells detached due to trauma.
Zoellner
H
H
Institute for Vascular Biology and Thrombosis Research, University of Vienna, Austria.
Höfler
M
M
Beckmann
R
R
Hufnagl
P
P
Vanyek
E
E
Bielek
E
E
Wojta
J
J
Fabry
A
A
Lockie
S
S
Binder
B R
BR
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003488:Cyanogen Bromide / Q000494:pharmacology; D004247:DNA / Q000032:analysis; D004229:Dithiothreitol / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D006801:Humans; D008854:Microscopy, Electron; D011994:Recombinant Proteins / Q000494:pharmacology; D012709:Serum Albumin / Q000187:drug effects / Q000494:pharmacology*; D012867:Skin / Q000098:blood supply; D014471:Umbilical Veins
D011994:Recombinant Proteins; D012709:Serum Albumin; D004247:DNA; D003488:Cyanogen Bromide; D004229:Dithiothreitol