| Project/Area Number |
16591657
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Osaka University |
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Principal Investigator |
TAHARA Masahiro Osaka University, Graduate School of Medicine, Assistant, 医学系研究科, 助手 (00294091)
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| Co-Investigator(Kenkyū-buntansha) |
TASAKA Keiichi Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (50155058)
SAKATA MASAHIRO Osaka University, Hospital, Associate Professor, 医学部附属病院, 助教授 (10260639)
OHMICHI MASAHIDE Osaka University, Graduate School of Medicine, Lecturer, 医学系研究科, 講師 (10283764)
MINEKAWA RYOKO Osaka University, Hospital, Assistant, 医学部附属病院, 助手 (10359838)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | preeclampsia / vasoconstriction / endothelial dysfunction / monomeric G protein / Rho / Rho-kinase |
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| Research Abstract |
Edema and vascular leakage play a part in the pathogenesis of preeclampsia, and serum from preeclamptic patients increases endothelial cell permeability. We examined a possible involvement of Rho-kinase signal-transduction pathways in the mechanisms of endothelial-cell permeability.
Cultured human umbilical vein endothelial cell (HUVEC) monolayers were used and permeability was measured by albumin flux and transendothelial electrical resistance (TER) of HUVEC monolayers. The possible involvement of Rho-kinase signaling was examined with the inhibitor, Y-27632. We also examined the effects of serum from patients with preeclampsia on the localization of VE-cadherin in HUVEC monolayers.
Our data demonstrated that (1) Serum from preeclamptic women increased endothelial permeability significantly (by 100%, p<0.01), while serum from normotensive pregnant women and non-pregnant women had no effect, (2) Y-27632 (10-6 mol/L) inhibited the increase in permeability induced by serum from preeclamptic patients, (3) Serum from preeclamptic patients induced a translocation of VE-cadherin within the cells, and (4) Inhibition of Rho-kinase by Y-27632 abolished the changes of intracellular localization of VE-cadherin induced by serum from preeclamptic patients.
These results suggested that serum from preeclamptic patients contains s factor or factors that increase endothelial-cell permeability, and the effect of preeclamptic serum may be Rho-kinase and VE-cadherin. Rho-kinase could be used as a new therapeutic target for treatment of preeclampsia.
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