Precision medicine for cardiovascular diseases by targeting clonal hematopoiesis of indeterminate potential via fetal programming

通过胎儿编程靶向不确定潜力的克隆造血，治疗心血管疾病的精准医学

• 批准号: 21K08037
• 负责人: 山田 浩之
• 金额: $ 2.58万
• 依托单位: Kyoto Prefectural University of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2021
• 资助国家: 日本
• 起止时间: 2021-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-21K08037/
• 关键词: 母体高脂肪食; エピジェネティクス; 胎児プログラミング; 腹部大動脈瘤; マクロファージ; 炎症; CHIP

胎生期の栄養状態や母体環境が成人期の心血管疾患罹患率に影響することは、胎児プログラミングとしてこれまでに報告されており、エピジェネティック修飾は心血管疾患や代謝疾患、悪性腫瘍の新たな治療法として注目されている。母体の高脂肪食摂取により、出生児の成人期にはマクロファージによる炎症反応によって動脈硬化の進展やインスリン抵抗性を引き起こすことが示されてきた。腹部大動脈瘤(AAA)は世界的に最も有病率の高い動脈硬化性疾患の一つであり、その発症はマクロファージの増加や炎症反応と密接に関係している。本研究では、高脂肪食を与えた母体由来マウス仔の、胎児プログラミングを介したマクロファージの破骨様細胞への形質変化が、AAAを増悪させるメカニズムについて解析を行った。本研究の結果より、母体の高脂肪食負荷が出生マウス仔の成体期におけるAAAの増悪に深く関与していることが示された。そのメカニズムとして、エピジェネティックな機序によりBMDMでのNFATc1の発現が促進されることで、破骨細胞様マクロファージへの分化が亢進する結果、MMPの発現が亢進していることが示唆された。本研究の成果は、胎児プログラミングによるマクロファージ形質変化の新たなメカニズムとしてH3K27me3を介したNFATc1の活性化に着目しており、AAAのみならず、出生マウス仔の心血管系疾患の進展を制御する新たな医療の構築に繋がる可能性を含有していると考えられた。

The incidence of cardiovascular disease in the maternal environment during the fetal period, the incidence rate of cardiovascular disease in the adult period, the incidence rate of cardiovascular disease in the adult stage, the incidence rate of cardiovascular disease in the maternal environment in the adult period, the incidence rate of cardiovascular disease in the adult environment, the incidence rate of cardiovascular disease in the adult environment, the incidence rate of cardiovascular disease in the adult environment, the incidence rate of cardiovascular disease in the adult environment, the incidence rate of cardiovascular disease in the adult environment, the incidence rate of cardiovascular disease in the adult environment, the incidence rate of cardiovascular disease in the adult environment, the incidence rate of cardiovascular disease in the adult environment, the incidence rate of cardiovascular disease in the adult environment, the incidence rate of cardiovascular disease in the adult environment, the incidence of cardiovascular disease in the adult environment, the incidence rate of cardiovascular disease in the adult environment, the incidence rate of cardiovascular disease in the adult environment, the incidence rate of cardiovascular disease in the adult The maternal diet is high in fat, and the maternal diet is high in fat. During the adult period of birth, there is no sign of inflammation, anti-inflammation, anti-inflammatory, progressive inflammatory sclerosis, anti-inflammatory, anti-inflammatory, anti- Large abdominal motor tumor (AAA) is the most morbidity in the world. Sclerosing disease is the most common disease in the world. In this study, the maternal origin of high-fat diet, high-fat diet and maternal parturient were studied. The maternal origin of the baby, the fetus, the mother, the baby, the baby, the mother, the The results of this study showed that the maternal diet with high fat diet showed that the baby was born with a high fat diet and the baby was born into adulthood. the results of this study showed that the maternal diet with high fat diet showed that the baby was born with a high fat diet. The results of this study showed that the maternal diet with high fat diet showed that the baby was born with a high fat diet. The results showed that the differentiation of bone marrow cells was increased, and that of MMP was detected. The results showed that the results of BMDM test showed that there was an increase in differentiation, and there was an increase in the rate of differentiation of bone marrow. In this study, the results of this study, the results of this study,

项目成果

Maternal High-Fat Diet Promotes Abdominal Aortic Aneurysm Expansion in Adult Offspring by Epigenetic Regulation of IRF8-Mediated Osteoclast-like Macrophage Differentiation.

母体高脂饮食通过表观遗传学调节IRF8介导的骨细胞状巨噬细胞分化来促进成人后代的腹部主动脉瘤扩展。

• DOI: 10.3390/cells10092224
• 发表时间: 2021-08-27
• 期刊: Cells
• 影响因子: 6
• 作者: Saburi M;Yamada H;Wada N;Motoyama S;Sugimoto T;Kubota H;Miyawaki D;Wakana N;Kami D;Ogata T;Matoba S
• 通讯作者: Matoba S