Phytoestrogen α-Zearalanol Attenuates Homocysteine-Induced Apoptosis in Human Umbilical Vein Endothelial Cells

الملخص EN

Hyperhomocysteinemia is an independent risk factor for cardiovascular diseases.

The enhanced nitrative stress plays an important role in homocysteine-induced endothelial dysfunction.

Previous studies have showed that phytoestrogen α-zearalanol alleviated endothelial injury in ovariectomized hyperhomocysteinemic rats; however, the underlying mechanism remains to be clarified.

This study was to investigate the effects of α-zearalanol on homocysteine-induced endothelial apoptosis in vitro and explore the possible role of nitrative stress in these effects.

Results showed that homocysteine (500 μmol/L, 24 h) induced the apoptosis of human umbilical vein endothelial cells (HUVECs) obviously, and this effect was significantly attenuated by pretreatment with α-zearalanol (10−8~10−6 mol/L).

Moreover, α-zearalanol downregulated proapoptotic protein Bax, upregulated antiapoptotic proteins Bcl-2 and Bcl-XL, and decreased the expression and activity of caspase-9.

These findings demonstrated that α-zearalanol could effectively alleviate homocysteine-induced endothelial apoptosis, and this antiapoptosis effect might be related to the inhibition of the intrinsic pathway.

Western blot indicated an enhanced 3-nitrotyrosine expression in HUVECs when challenged with homocysteine, which was attenuated by pretreatment with α-zearalanol.

This result implied that inhibition of nitrative stress might play a role in the protective effect of α-zearalanol on endothelial cells.

Such discovery may shed a novel light on the antiatherogenic activities of α-zearalanol in hyperhomocysteinemia.