2001 Fiscal Year Final Research Report Summary
Mechanism of anti-atherosclerotic effect of estrogen
Grant-in-Aid for Scientific Research (B)
|Allocation Type||Single-year Grants |
Obstetrics and gynecology
|Research Institution||Osaka University |
MORISHIGE Kenichiro Osaka University Graduate School of Medicine, Assistant professor -> 大阪大学, 医学系研究科, 助手 (90283788)
OHMICHI Masahide Osaka University Graduate School of Medicine, Assistant professor, 医学系研究科, 助手 (10283764)
SAKATA Masahiro Osaka University Graduate School of Medicine, Lecturer, 医学系研究科, 講師 (10260639)
|Project Period (FY)
1999 – 2001
|Keywords||estradiol / IMT / estrogen receptor / PDGF / eNOS / atherosclerosis / P-selection / パルスドップラー|
Atherosclerotic cardiovascular disease (CVD) is the major cause of morbidity and mortality in postmenopausal women. Estrogens have been shown to inhibit atherosclerosis and to help maintaining arterial function.
Measurement of intima-media thickness (IMT) of the carotid artery is used in pathophysiological studies of the atherosclerotic process to search the factors initiating the early development of atherosclerosis in the carotid arteries.
IMT in the ERT group patients showed a significant decrease during HRT period in both mean and maximum IMT, while the control group patients showed no statistically significant change. Lipid metabolism markers and P-selection showed significant decrease in the longitudinal analysis. These data are under submission (Nishio et al.).
In vitro study:
In studies of human umbilical vein endotherial cells and SV40-transformed rat lung vascular endotherial cells, 17β-estradiol (E2), but not 17α-E2, caused acute activation of eNOS that was unaffected by actinomycin D and was specifically blocked by the pure estrogen receptor antagonist ICI-182,780. Furthermore, 17α-E2 induced eNOS activation through an Akt-dependent mechanism, which is mediated by Erαvia a nongenomic mechanism (Hisamoto et al.).
In vascular smooth muscle cells, E2 suppressed PDGF-induced cell proliferation. But, the detailed mechanism of anti-proliferative effect of E2 is under investigation.
Research Products (1 results)
[Publications] K Hisamoto, M Ohmichi, H Kurachi, J Hayakawa, Y Kanda, Y Nishio, K Adachi, K Tasaka, E Miyoshi, N Fujiwara, N Taniguchi, Y Murata: "Estrogen induces the Akt-dependent activation of endothelial nitric-oxide synthase in vascular endothelial cells"J Biol Chem. 276 (5). 3459-3467 (2001)