| Project/Area Number |
15K09138
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Cardiovascular medicine
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
桑原 宏一郎 信州大学, 学術研究院医学系, 教授 (30402887)
中川 靖章 京都大学, 医学研究科, 助教 (70452357)
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| Co-Investigator(Renkei-kenkyūsha) |
Minamino Naoto 国立循環器病研究センター, オミックスセンター, センター長 (50124839)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 心不全 / BNP / poBNP / 前駆体 / O型糖鎖修飾 / プロセシング / 心筋細胞 / macro-proBNP / proBNP / 急性心不全 / microRNA-30 / GALNT |
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| Outline of Final Research Achievements |
We introduced human proBNP gene into rat cardiac myocytes and assessed the processing of proBNP by measuring proBNP and total BNP levels using our developed chemiluminescent immunoassay in the culture medium. We also produced proBNP mutant and assessed the effect of each glycosylation site on the proBNP processing. We found that Th71 and Th48 directly inhibit the processing of proBNP, and that other five glycosylation sites were indirectly associated with the inhibition of processing of proBNP. We also showed that the proBNP/total BNP ratio was higher and cGMP/total BNP ratio was lower in severe chronic heart failure compared with mild chronic heart failure. We experienced a case of heart failure whose BNP level was more than 35000pg/mL. We elucidated the mechanism of it and first reported it in the world as a case of macro-proBNP.
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