2021 Fiscal Year Final Research Report
Roles of sex chromosomes in pathophysiological sex difference formation in the heart
| Project/Area Number |
20K21487
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 47:Pharmaceutical sciences and related fields
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| Research Institution | University of Shizuoka |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
森本 達也 静岡県立大学, 薬学部, 教授 (50390779)
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| Project Period (FY) |
2020-07-30 – 2022-03-31
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| Keywords | 性差 / 心臓 / 血管 / 性決定遺伝子 / iPS細胞 / 2卵性双生児 |
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| Outline of Final Research Achievements |
To understand the roles of sex chromosome in the sex differences pathogenesis of cardiovascular diseases, we performed morphofunctional analysis of fetal mouse hearts and establishment of human iPS cell lines from the blood of male and female dizygotic twins. In hearts removed from embryonic mice in late gestation, we developed an original coronary angiography technique and revealed sex differences in coronary artery vessel diameter and drug responsiveness. Analysis of gene expression in male and female embryonic murine hearts identified genes that escape the X chromosome inactivation mechanism, suggesting a link to the morphofunctional sex differences found in this study. To further elucidate the mechanism of sex differences, iPS cells were established from blood of males and females of the same age with similar genetic backgrounds.
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| Free Research Field |
薬理学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究成果は発生期心臓の性差の一端を明らかにしたことから、心血管病の発症・病態における理解が進んだ点が学術的意義である。また、ヒトiPS細胞を用いて、実験動物で得られた仮説をヒトで検証することを目指している点も特徴である。なお、心血管病は更年期以降に患者数が爆増し、性ホルモンだけではない性差のメカニズムを理解することは、超高齢化社会における人々の疾患予防・健康対策を考える際の情報基盤となると期待できる。
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