The soyabean isoflavone genistein modulates endothelial cell behaviour

The aim of the present study was to investigate the direct action of the phyto-oestrogen genistein (Gen) on vascular endothelial behaviour, either in the presence or absence of proinflammatory agents. In rat aortic endothelial cell (EC) cultures, 24 h of treatment with Gen significantly increased cell proliferation in a wide range of concentration (0.001-10 nm). This mitogenic action was prevented by the oestrogen receptor (ER) antagonist ICI 182780 or by the presence of the specific NO synthase inhibitor l-nitro-arginine methyl ester. When monocytes adhesion to EC was measured, Gen partially attenuated leucocyte adhesion not only under basal conditions, but also in the presence of bacterial lipopolysaccharides (LPS). The effect of the phyto-oestrogen on the expression of EC adhesion molecules was evaluated. Gen down-regulated the enhancement in mRNA levels of E-selectin, vascular cell adhesion molecule-1 and P-selectin elicited by the proinflammatory agent bacterial LPS. The regulation of EC programmed death induced by the isoflavone was also demonstrated. Incubation with 10 nm Gen prevented DNA fragmentation induced by the apoptosis inductor H2O2. The results presented suggest that Gen would exert a protective effect on vascular endothelium, due to its regulatory action on endothelial proliferation, apoptosis and leucocyte adhesion, events that play a critical role in vascular diseases. The molecular mechanism displayed by the phyto-oestrogen involved the participation of the ER and the activation of the NO pathway.