低调LATS1/2驱动内皮衰老相关的干部 (SAS) 和动脉瘤损伤形成
bioRxiv : the preprint server for biology
|July 16, 2025
概括
内皮细胞中LATS1/2的损失会触发与衰老相关的干细胞 (SAS) 状态,促进动脉血症. 向CD38可能为急性冠状动脉综合征患者的血管功能障碍和斑块不稳定提供治疗策略.
科学领域:
- 血管生物学 血管生物学
- 动脉血症的分子机制
- 细胞衰老 细胞衰老
背景情况:
- 动脉血症是急性冠状动脉综合征 (ACS) 的关键事件,与血液流动 (d-flow) 受到干扰有关.
- 河马路径激酶LATS1/2参与机械应激反应,但它们在d流诱导的动脉血症中的作用尚不清楚.
研究的目的:
- 为了研究内皮细胞 (EC) 特定的LATS1/2在动脉血症中的作用.
- 为了阐明分子机制,通过干扰血液流动诱导通过ECs的动脉血症.
主要方法:
- 在部分左冠状动脉结 (PLCL) 模型中利用了EC特异性淘汰赛 (EKO) 小鼠.
- 进行了斑块空间多奥米克分析,集成成像质细胞计,序列免疫光 (COMETTM) 和空间代谢学.
主要成果:
- 在EC中LATS1/2删除诱导了与衰老相关的干性 (SAS) 现型,其特征是CD38上调和减少硫酸盐氧化酶 (SUOX) 活性.
- 代谢障碍,包括线粒体功能的改变和增强的谷氨酸/TCA循环代谢,尽管ATP耗尽,但持续的EC增殖.
- CD38抑制减弱了动脉血性斑块的形成,在人类斑块中观察到类似的EC表型.
结论:
- 在EC中LATS1/2的损失驱动SAS,促进EC的增殖,衰老和脆弱的新血管化,这些都是动脉血症的特征.
- 确定了LATS1/2-CD38-SUOX轴作为一种新的途径,可以调节SAS驱动的动脉血栓塞.
- 向CD38为ACS中的血管功能障碍和斑块不稳定性提供了潜在的治疗策略.
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