MAT2A通过调解巨细胞的表观遗传重编程来促进动脉样硬化斑块的脆弱性
Zhuo Du1,2, Pingping Wan1,2, Manyu Du1,2
1Department of Cardiology, the 2nd Affiliated Hospital of Harbin Medical University, Harbin, China.
Nature communications
|December 16, 2025
概括
单细胞中的甲氨酸代谢与易受动脉样硬化斑块有关. 向MAT2A酶可以减少炎症和斑块脆弱性,为心血管疾病提供潜在的治疗策略.
科学领域:
- 心血管生物学 心血管生物学
- 代谢重编程 代谢重编程
- 动脉样硬化病原体的产生
背景情况:
- 动脉样硬化包括由单细胞和巨细胞驱动的慢性炎症.
- 氨酸代谢在单细胞/巨细胞炎症和动脉样硬化中的作用尚未完全理解.
研究的目的:
- 调查单细胞氨酸代谢与脆弱的动脉样硬化斑块之间的联系.
- 为了阐明甲胺腺转移酶IIα (MAT2A) 在动脉样硬化进展中的作用.
主要方法:
- 非向代谢学和质谱学用于分析单细胞代谢.
- 胰冠状动脉光学连贯断层扫描以识别脆弱斑块 (TCFA).
- 表观遗传特征 (H3K4me3) 和遗传/药物抑制MAT2A.
主要成果:
- 单细胞氨酸代谢与TCFA存在相关.
- 在动脉样硬化中MAT2A的表达很高,并在炎症基因促进者上调解H3K4me3的丰富.
- 抑制或消去MAT2A,以及低氨酸饮食,减少炎症和斑块脆弱性.
- 上腺素通过mTOR-c-MYC轴上调节MAT2A.
结论:
- 通过MAT2A介导的甲氨酸代谢是单细胞/巨细胞炎症和动脉样硬化中的斑块脆弱性的关键驱动因素.
- MAT2A代表了治疗动脉样硬化的有前途的治疗标.
- 结合的上腺素和氨酸代谢会影响TCFA和临床结果.
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