| Project/Area Number |
09470177
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | The University of Tokyo |
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Principal Investigator |
KATO Hltoshi (2000) The University of Tokyo, Facoulty of Medicin, Lecturer, 医学部・附属病院, 講師 (70214393)
柳澤 正義 (1997-1999) 東京大学, 医学部・付属病院, 教授 (90049031)
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| Co-Investigator(Kenkyū-buntansha) |
ANDO Joji The University of Tokyo school of medicine Professor, 大学院・医学系研究科, 教授 (20159528)
賀藤 均 東京大学, 医学部・附属病院, 講師 (70214393)
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| Project Period (FY) |
1997 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥12,600,000 (Direct Cost: ¥12,600,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1998: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1997: ¥7,400,000 (Direct Cost: ¥7,400,000)
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| Keywords | Pulmonary hypertension / Endothelial cells / Shear stress / Stretch / Vascular compliance / Molecular biology / 血圧 |
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| Research Abstract |
Endothelial dysfunction secondary to altered hemodynamic forces is considered as an important factor in development of secondary pulmonary hypertension. However, endothelial responces to combined hemodynamic forces are still unclear. To investigate the effects of combined hemodynamic forces on endothelial cells (ECs). we developed a new apparatus that allows ECs to be subjected to various levels of shear stress, pressureand cyclic stretch, and examined the synergistic effects of these forces on endothelin (ET) and nitric oxide synthase (eNOS) mRNA levels by RT-PCR.Shear stress decreased the ET mRNA levels HUVECs, but in contrast increased the ET mRNA levels in HUVECs. Pressure accompanied with cyclic stretch (10%, 1Hz) increased the ET mRNA.Shear stress increased the eNOS mRNA levels in HUVECs, while neither pressure nor cyclic stretch had any effect. These results indicate that ET mRNA level was regulated by combined mechanical forces, during the eNOS mRNA level was regulated mainly b
… More
y shear stress, and ECs had different mechanism to regulate ET mRNA expression according to the direction of the hemodynamic forces. Then we performed luciferase assay of ET promotor region to determine the cis-elemet to regulate the ET mRNA expression. Deletion analysis and Mutagenesis analysis showed NF-kappa B concensus sequence which located at-2.8kB had an important role in shear stress dependent ET mRNA suppression, and another region 2.5kB downstream of this site act as an enhancer of the pressure dependent ET mRNA expression.
In this study, it was also found Windkessel model, which utilizes the compliance and resistance as parameters, is useful in understanding the pulmonary arterial compliance in pediatric patients with congenital heart disease. Cp (pulmonary artery diastolic compliance) calculated by the exponential portion and by the full diastolic wave of MPA diastolic pressure wave forms were well correlated. Normal value of Cp was estimated and found a significantly low Cp in VSD/PH.Cp can be one of the parameters for assessing pulmonary hypertension and thus help in surgical decision making of children with septal defects. Less
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