Atheroprotective effect of estriol and estrone sulfate on human vascular smooth muscle cells.
In patients with atherosclerosis, fibrosclerotic focuses are induced by multiplication of vascular smooth muscle cells (VSMC), and they are regulated by cytokines and regulators. There have been few reports about the atheroprotective effect of estriol (E(3)). Estrone sulfate (E(1)-S) is the predominant estrogen of conjugated equiline estrogens, which is commonly used in hormone replacement therapy, but it should be hydrolyzed by steroid sulfatase (STS) 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 atheroprotective effects like E(2). First, we detected the presence of STS mRNA in VSMC 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 TGF-beta, in VSMC, in the presence and absence of E(3) and estrogens. As a result, the expression 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 was 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 cytokines 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 atherogenesis.
Kikuchi
N
N
Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, Japan. nkikuchi@koto.kpu-m.ac.jp
Urabe
M
M
Iwasa
K
K
Okubo
T
T
Tsuchiya
H
H
Hosoda
T
T
Tatsumi
H
H
Honjo
H
H
D001161:Arteriosclerosis / Q000201:enzymology / Q000517:prevention & control*; D001192:Arylsulfatases / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D004958:Estradiol / Q000494:pharmacology; D004964:Estriol / Q000494:pharmacology* / Q000627:therapeutic use; D004970:Estrone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D017403:In Situ Hybridization; D007375:Interleukin-1 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D043266:Steryl-Sulfatase; D016212:Transforming Growth Factor beta / Q000235:genetics
D007375:Interleukin-1; D015850:Interleukin-6; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D004970:Estrone; D004958:Estradiol; D001192:Arylsulfatases; D043266:Steryl-Sulfatase; D004964:Estriol; C017296:estrone sulfate