Inhibition of microvascular endothelial apoptosis in tissue explants by serum albumin

Plasma factors appear to inhibit endothelial cell (EC) apoptosis in vivo so that now influences microvascular form. The identity of these factors has not, however, been established. Earlier, we reported that apoptosis in isol ated, serum-deprived human EC is inhibited by albumin (Alb). Here, we demon strate likely biological relevance of this to vascular remodelling in exper iments with tissue explants. Rat skin explants were incubated in medium M19 9 with or without serum, bovine Alb, or human Alb. EC in paraffin sections of explants were labelled by lectin histochemistry and the relative proport ion of apoptotic was EC determined. Apoptosis was confirmed by transmission electron microscopy and terminal deoxynucleotidyl transferase labelling. S erum-free culture induced EC apoptosis (P < 0.02) and this was strongly inh ibited by Alb at physiological concentrations (P < 0.01). This was not a no nspecific protein effect, as mercaptoethanol denaturation destroyed the act ivity and ovalbumin was not protective. Also, protection was not due to ser um contaminants, as recombinant human Alb had activity identical to that of native material. The dose response was identical for all Alb preparations tested, with maximal activity at physiological concentrations. Protection w as not limited to rat tissue as similar results were obtained with human gi ngival explants. These data support a role for Alb as a plasma antiapoptoti c factor for EC in tissues, (C) 1999 Academic Press.