母亲高水平的甘氨酸会增加子女患上心房隔膜缺陷的风险
Ya-Nan Qiao1, Wei-Cheng Chen2, Yu-Ling Chen3
1Institute for Developmental and Regenerative Cardiovascular Medicine, MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing, China.
JACC. Basic to translational science
|June 25, 2025
概括
母亲的糖氨酸升高,与遗传变异有关,增加了子孙的心房隔膜缺陷 (ASD) 风险. 这通过 lysine-glycylation 发生,这种过程抑制了关键的心脏信号通路.
科学领域:
- 发展生物学 发展生物学
- 遗传学 是一个遗传学.
- 生物化学 生物化学
背景情况:
- 氨基酸失衡与先天性心脏病 (CHD) 风险有关.
- 特定的遗传变异可能会影响氨基酸代谢和发育结果.
研究的目的:
- 为了研究特定的遗传变异 (rs2545801 C/C),母体甘氨酸水平和心房隔膜缺陷 (ASD) 之间的联系.
- 探索高水平甘氨酸影响心脏发育的分子机制.
主要方法:
- 对携带rs2545801 C/C变异的女性进行基因型分析.
- 在怀孕第一季度与ASD风险之间对母体甘氨酸水平的相关性分析.
- 动物研究涉及给孕小鼠高糖氨酸饮食.
- 在心脏内皮细胞中对TEK受体氨酸激酶信号的分子分析.
主要成果:
- 患有rs2545801 C/C基因型的女性的甘氨酸水平较高,后代患ASD的风险更高.
- 在怀孕早期,母亲的高血糖水平与ASD发病率的增加相关.
- 在怀孕的小鼠中,高甘氨酸饮食增加了它们后代的ASD风险.
- 升高的甘氨酸导致TEK受体的氨酸糖化增加,抑制了TEK-PI3K-AKT/FOXO1信号传输.
结论:
- 受到rs2545801 C/C基因型影响的母体糖氨酸升高是心房隔膜缺陷的危险因素.
- TEK受体的 lysine-glycylation 是一种关键的机制,可以调解由甘氨酸诱导的致性.
- 准 lysine-glycylation 路径可能为预防 ASD 提供一种新的治疗策略.
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