Effects of phytoestrogens on DNA synthesis and creatine kinase activity in vascular cells

Background: The aim of this study was to assess the effect of phytoestrogens on the human vascular wall in vi I ro. Methods: We compared the effects of E-2 to those of genistein (G). daidzein (D), biochanin A (BA), equol (EQ), and quecertin (Qu) on (3)[H] thymidine incorporation and creatine phosphokinase (CK) activity in human vascular smooth muscle cells (VSMC) and in a human endothelial cell line (E304). Results: in VSMC. E-2, the estrogen antagonist raloxifene (RAL). G. and D stimulated DNA synthesis at low concentrations and suppressed (3)[H] thymidine incorporation at higher concentrations. In contrast. BA and EQ had a monophasic stimulatory effect on (3)[H] thymidine incorporation (87% +/- 9% and 54% +/- 17%, respectively) whereas Qu had only an inhibitory effect (-36 +/- 1617c at 30 nmol/L). In E304 cells, all phytoestrogens stimulated DNA synthesis in a dose-related manner. In both cell types E-2, RAL as well as all phytoestrogens increased CK-specific activity. The administration of phytoestrogens to immature female rats resulted in increased CK in the aorta (Ao) (60% to 220%) and in the left ventricle of the heart (Lv) (45% to 16%). Similar increases in Ao and Lv CK were also induced by E-2 and all five phytoestrogens in ovariectomized (OVX) female rats. RAL antagonized phytoestrogen-induced CK activity in human vascular cells and in the rat Ao and Lv tissue but did not block phytoestrogen effects oil DNA synthesis in human VSMC. Conclusions: Although phytoestrogens have estrogen-mimetic effects oil cell growth and CK in cultured human vascular cells and oil CK in rat vascular tissues in vivo, the effects on human VSMC replication are highly dependent oil the concentration and the particular phytoestrogen under investigation. (C) 2001 American Journal of Hypertension, Ltd.