| Project/Area Number |
20KK0196
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| Research Category |
Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 53:Organ-based internal medicine and related fields
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| Research Institution | The University of Tokyo (2023)
Jichi Medical University (2020-2022) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
砂河 孝行 自治医科大学, 医学部, 講師 (40418637)
仙波 宏章 自治医科大学, 医学部, 客員研究員 (80747923)
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| Project Period (FY) |
2020-10-27 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000)
Fiscal Year 2023: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2022: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2021: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2020: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | VEGFA / マクロファージ / 心筋細胞 / 血管新生 / ワクチン / 組織線維化 / 心臓病 / がん / 血管内皮細胞増殖因子 / VEGF-A / 心臓 / 血管 / VEGF / リモデリング |
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| Outline of Research at the Start |
がんに対する化学療法は近年大きく進歩し、がん患者の予後を大幅に改善しています。一方で化学療法に伴って、心臓病や高血圧症など、いわゆるがん関連心臓病を発症することが多いことが判ってきました。本研究はがん治療で標的とされている細胞内シグナルに着目し、それらが心臓や血管系に果たしてる役割を明らかにしていくことで、がん関連心臓病の病態を理解し、その予防法の開発を目指します。
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| Outline of Final Research Achievements |
It is not well-understood how cancer-bearing status and cancer chemotherapy cause heart disease. We studied the VEGFA function in the heart to reveal the mechanism of cancer chemotherapy-related cardiotoxicity. We found that although cardiomyocytes produced the majority of VEGFA in an adult murine heart, the deletion of cardiomyocyte-derived VEGFA did not affect its function. The amount of myeloid cell-derived VEGFA is significantly small, however, deletion of VEGFA in myeloid cells disrupts vascular integrity and left ventricular systolic function. These results suggest that we wonder if angiogenesis inhibitors cause cardiotoxicity by suppressing macrophage-derived VEGFA signaling. In addition, we developed vaccination based therapy against tissue fibrosis in the cooperative study with Prof. Stockmann at Zurich University. It is likely that vaccination-based immunotherapy will become a preventive approach to the cardiotoxicity caused by cancer chemotherapy.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究成果により、血管新生阻害薬による心毒性発症機序が明らかとなることでがん化学療法を行う際に心臓の炎症状態が血管新生阻害薬投薬の判断基準となり得る。また、抗線維化ワクチンの開発は、がん化学療法関連心毒性の予防を可能とし、抗がん剤の安全な継続治療を推し進めることが容易となることでがん化学療法の治療効果を向上させることが期待される。
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