Atheroprotective effect of estriol and estrone sulfate on human vascular smooth muscle cells

In patients with atherosclerosis, fibrosclerotic focuses are induced by mul tiplication of vascular smooth muscle cells (VSMC), and they are regulated by cytokines and regulators. There have been few reports about the atheropr otective effect of estriol (E-3) Estrone sulfate (E-1-S) is the predominant estrogen of conjugated equiline estrogens, which is commonly used in hormo ne replacement therapy, but it should be hydrolyzed by steroid sulfatase (S TS) to enter the cells of target tissues. The purpose of this study was to detect STS in VSMC and to investigate whether E-3 and E-1-S have atheroprot ective effects like E-2. First, we detected the presence of STS mRNA in VSM C by in situ hybridization. We then examined the changes in the expression of mRNAs of cytokines, namely, PDGF-A chain, IL-1, IL-6 and TCF-beta, in VS MC, in the presence and absence of E-3 and estrogens. As a result, the expr ession of PDGF-A chain, IL-1 and IL-6 mRNAs was suppressed by E-3 (P < 0.05 VS control) significantly like E-1-S and E-2, but that of TGF-beta mRNA wa s not significantly affected by any estrogen. These results indicate that E -1-S can be hydrolyzed by STS in VSMC, and that E-3 may regulate the cytoki nes by suppressing the production of mRNAs. It is suggested that there is a possibility of E-1-S and E-3 having a direct effect on vessels in atheroge nesis. (C) 2000 Elsevier Science Ltd. All rights reserved.