希斯脱乙酶3对内皮细胞存活和动脉样硬化发育至关重要,以应对流动干扰
Anna Zampetaki1, Lingfang Zeng, Andriana Margariti
1Cardiovascular Division, King's College London BHF Centre, London, UK.
Circulation
|December 23, 2009
概括
基斯脱乙酶3 (HDAC3) 对于内皮细胞的存活和完整性至关重要,特别是在血液流动受损的情况下. 它的缺失导致严重的动脉样硬化和血管破裂,突出其保护作用.
科学领域:
- 心血管生物学 心血管生物学
- 分子生物学分子生物学
- 动脉样硬化研究 动脉样硬化研究
背景情况:
- 在成熟的内皮细胞中,希斯脱乙酶3 (HDAC3) 的功能尚不清楚.
- 众所周知,HDAC3对于内皮原生细胞分化至关重要.
- 这项研究研究了HDAC3在维持内皮完整性方面的作用,在血液流动受损的区域中,这些区域容易发生动脉样硬化.
研究的目的:
- 阐明HDAC3在成熟内皮细胞中的功能.
- 为了确定HDAC3在在血液流动受损的情况下维护内皮完整性的作用.
- 研究HDAC3影响内皮细胞存活率和动脉样硬化发展的机制.
主要方法:
- 对动脉样硬化症的阿波利波蛋白E-Knockout小鼠模型.
- 面部染色和大动脉异体移植实验.
- 在体外内皮细胞培养暴露于流动干扰.
- 使用lentiviral载体 (shHDAC3) 进行HDAC3淘汰.
- 共同免疫沉和西部斑分析以研究蛋白质相互作用和修饰.
主要成果:
- 在体内和体外干扰流域中,HDAC3的表达被上调.
- 干扰的流动会通过Akt相互作用诱导HDAC3的转录后修饰和稳定.
- 降低HDAC3导致内皮细胞存活率降低,亡增加,以及严重的动脉样硬化病变形成.
- shHDAC3处理的大动脉异位移植显示底层膜破坏和血管破裂,一些移植迅速失败.
结论:
- HDAC3 作为内皮细胞的基本生存分子.
- 通过Akt激活,HDAC3保持了内皮完整性.
- 在apolipoprotein E-knockout小鼠中失去HDAC3功能会导致严重的动脉样硬化和血管破裂.
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