Study of sugar chains binding to BNP precursors; 1. Structure analysis, 2. Molecular mechanism, 3. relationship with heart failure condition

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08103
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Kyoto University
• Principal Investigator: Nishikimi Toshio 京都大学, 医学研究科, 非常勤講師 (80291946)
• Co-Investigator(Kenkyū-buntansha): 中川 靖章 京都大学, 医学研究科, 助教 (70452357)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 心不全 / BNP / proBNP / 糖鎖修飾 / 分子型

Outline of Final Research Achievements

The current assay for BNP system cross-reacts precursor proBNP, indicating that BNP means proBNP + BNP (= total BNP). The applicant created a new assay system for the proBNP and total BNP, which enabled the measurement of the proBNP / total BNP ratio and showed that this ratio was higher in severe chronic heart failure patients. When we examined the proBNP / total BNP ratio in acute heart failure, we found the proBNP / total BNP ratio was lower in mild heart failure, which make cGMP / BNP ratio increasing to compensate for heart failure. Deteriorating renal function during treatment for acute heart failure is well known sign for poor prognosis. Therefore, early detection is important. In this study, we found that the NT-proBNP / mature BNP ratio increased preceding to the deterioration of renal function in acute heart failure patients.

Free Research Field

循環器内科学

Academic Significance and Societal Importance of the Research Achievements

急性心不全の代償機構としてproBNP/total BNP比率を下げて代償することは新規の機序であり、今後の心不全の治療や診断に応用ができる可能性がある。proBNP/total BNP比率を決めているのはproBNPへの糖鎖修飾であり、糖鎖修飾の機序を解明することで心不全の患者の予後改善に結びつく可能性がある。急性心不全の治療中の腎機能悪化の早期発見の指標は、これまでたくさんの研究がなされてきたが、決定的なものはなかった。腎機能悪化を早期に予知するほど予防、治療のための介入も早くなり、心不全患者の予後の改善に結びつく可能性が高い。今回の研究で入院3日目に有意な変化が見出され期待できる。