| Project/Area Number |
16590728
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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 |
Circulatory organs internal medicine
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| Research Institution | National Cardiovascular Center Research Institute |
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Principal Investigator |
HINO Jun National Cardiovascular Center Research Institute, Head of Biochemistry, 生化学部, 室長 (40260351)
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| Co-Investigator(Kenkyū-buntansha) |
KANGAWA Kenji National Cardiovascular Center Research Institute, Deputy Director, 副所長 (00112417)
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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 |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2005: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2004: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | BMP-3b / cardiovascular system / arteriosclerosis / vascular calcification / vascular smooth muscle cell / 心血管系 |
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| Research Abstract |
BMP-3 was originally isolated from femur and have angatonistic activity against BMP-2 in osteoblast and developing embryos. Although BMP-3b gene was hightly expressed in aorta, its function is stll unkown in cardiovascular system. Regarding the BMPs funciton in cardiovascular systems, it had remained unclear. Since the paper which showed mutation of BMP receptor causesed PPH (primary pulmornary heypertension) was published in 2000, study of BMP in cardiovascular systeme is being in progress. To clarify the function of BMP-3b in cardiovascular system, first we examined the gene expression of BMP-3b in cardiovascular tissues (aorta and heart) and in cultured cells (vascular smooth muscle cells (VSMC) and maocyte cells). BMP-3b gene is highly expressed in aorta and expresssion level was not changed even in the aorta removed endothelial cells. This result showed that BMP-3b gene was expressed only in highly differentiated VSMC. This gene expression pattern was similar to that in osteoblast
… More
. In the heart, BMP-3b gene was expressed and the level of the expression was higher in atria than in ventricular. The function of other member of BMPs in atria was unclear, therfore to elucidate the activity of BMP-3b in atria is new observation of BMPs function. Next we examined the association of BMP-3b and cardiovascular disease. BMP-3b mRNA level was increased in rat cardiovascular pathologic condition, suggesting that BMP-3b might be involved in cardiovascular disease. The biological activity of BMP-3b was examined using adenovirus expression system. The result showed that BMP-3b tended to have growth promoting activity in VSMC, indicating that BMP-3b act as BMP-2 antagonist. This BMP-2 antagonistic activity is identical to that in developing embros and osteoblasts indicated above. We already reported that the BMP-3b activity was regulated by precursor processing and pro-form had different activity compared to mature form, indicating that processing of the BMP-3b precursor is critical process of the activity. We tried to identify this processing enzyme. Using the overexpression system in Xenopus embryo, we clarified that PC6 would be BMP-3b processing enzyme. Less
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