FAM49B由阿斯巴拉金内酶分裂促进血管光滑肌肉细胞在动脉新生中的迁移
Xuying Xiang1, Mengting Qin1, Lei Nie1
1Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (X.X., M.Q., L.N., X.G., J.C., D.J., L.M.).
Arteriosclerosis, thrombosis, and vascular biology
|June 26, 2025
概括
FAM49B片段促进血管光滑肌肉细胞迁移和动脉样硬化. 抑制FAM49B的阿斯巴拉金内酶 (AEP) 裂变可能为动脉样硬化提供治疗策略.
科学领域:
- 心血管生物学 心血管生物学
- 动脉样硬化的分子机制
背景情况:
- 血管光滑肌细胞 (VSMC) 迁移对于动脉样硬化发展至关重要,但潜在的分子通路仍然不清楚.
- 在动脉样硬化斑块中检测到FAM49B (序列相似性49成员B家族) 片段,促使对其作用进行调查.
研究的目的:
- 阐明FAM49B碎片在VSMC迁移和动脉生成中的作用.
- 研究FAM49B碎片影响动脉样硬化进展的机制.
主要方法:
- 使用了转基因小鼠模型 (Aep-/- ,Aep-/- Apoe-/- 和VSMC特定的FAM49B过度表达).
- 采用腺病毒基因转移用于FAM49B片段过度表达,并分析了AEP抑制剂 (化合物11) 的作用.
- 通过质谱测量识别了FAM49B碎片,并使用免疫光和免疫阻塞分析了它们在动脉样硬化斑块中的表达.
主要成果:
- 由AEP裂变产生的FAM49B片段在动脉样硬化病变和VSMC中被上调.
- 与全长FAM49B不同的是,FAM49B片段通过激活Rac1并诱导actin聚合,促进VSMC迁移.
- 过度表达FAM49B片段增加了小鼠的动脉样硬化负担,而AEP删除或AEP抑制减少了斑块大小.
结论:
- 来自AEP的FAM49B碎片增强了Rac1介导的VSMC迁移,从而促进了动脉样硬化.
- 针对AEP介导的FAM49B碎片化是一个潜在的动脉样硬化治疗策略.
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