在腹腔大动脉动脉瘤中,FAM3A通过调节KLF4无处不在的调节来重塑VSMC命运规范
Chuxiang Lei1, Haoxuan Kan1, Xiangyu Xian1
1Department of Vascular Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Dongcheng District, Beijing, 100730, China.
Nature communications
|September 2, 2023
概括
血管光滑肌细胞 (VSMC) 的分化是腹腔大动脉动脉瘤 (AAA) 的关键. 发现一种代谢性细胞因子FAM3A的AAA水平下降,其恢复维持了VSMC状态,抑制了AAA的进展.
科学领域:
- 心血管生物学 心血管生物学
- 细胞的新陈代谢
- 分子医学是分子医学.
背景情况:
- 血管光滑肌细胞 (VSMC) 的分化在腹腔大动脉动脉瘤 (AAA) 发病过程中至关重要.
- 在AAA中调节VSMC命运的分子机制仍然不完全理解.
研究的目的:
- 研究FAM3A,一种代谢性细胞因子,在AAA期间调节VSMC分化中的作用.
- 阐明FAM3A在AAA中影响VSMC命运的潜在分子机制.
主要方法:
- 在人类AAA组织,血和小鼠AAA模型中对FAM3A表达的定量分析.
- 在体内和体外实验中,涉及FAM3A过度表达和补充的实验.
- 评估VSMC分化状态和细胞亚群变化.
- 研究FAM3A对KLF4无处不在,酸化和核定位的影响.
主要成果:
- 在AAA患者和小鼠模型中,FAM3A表达显著降低.
- 通过保留差异化的VSMC表型,FAM3A过度表达或补充减弱了AAA形成.
- FAM3A抑制了VSMC分化为巨细胞,冠状细胞,骨质细胞,介质细胞和纤维细胞类细胞.
- FAM3A促进了KLF4的无处不在,降低了其酸化,并减少了其核转位.
结论:
- 在AAA中,FAM3A充当了VSMC命运的关键调节者.
- FAM3A的机制涉及调节KLF4的无处不在和稳定性.
- 向FAM3A可能提供一种治疗策略,以恢复AAA中的VSMC平衡.
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