由心脏压力过载引起的循环外体含有功能性 ангиотензин II 型 1 型受体
Gianluigi Pironti1, Ryan T Strachan1, Dennis Abraham1
1From Departments of Medicine (G.P., R.T.S., D.A., S.M.-W.Y., M.C., W.C., K.H., L.M., L.J.W., H.A.R.), Cell Biology (H.A.R.), and Molecular Genetics and Microbiology (H.A.R.), Duke University Medical Center, Durham, NC.
Circulation
|May 22, 2015
概括
对心脏的生物力学压力释放出含有血管新生素II型I受体 (AT1R) 的外体. 这些外体调节心血管功能和血压反应.
科学领域:
- 心血管生物学 心血管生物学
- 细胞生物学 细胞生物学
- 分子医学是分子医学.
背景情况:
- 生物力学力量在诱导外体分泌以调节心血管功能的作用中的作用尚不清楚.
- 外体是细胞间通信的关键媒介,携带功能性蛋白质和核酸.
- 血管激素II型I受体 (AT1R) 在心血管调节中起着至关重要的作用.
研究的目的:
- 研究含有 angiotensin II I型受体 (AT1R) 的外体的分泌和活性.
- 为了确定对心脏的生物力学力量是否可以诱导外体分泌.
- 探索AT1R含有的外体在心血管功能中的作用.
主要方法:
- 从暴露于透拉伸的细胞培养物中分离出外体,并从心脏压力过载的小鼠中分离出血清.
- 使用电子显微镜和放射性体受体结合试验证实AT1R在外体中的存在.
- 调查β-arrestin2在AT1R外体贩运和功能中的作用.
- 在体内研究中,使用小鼠进行了全球和心肌细胞特异性β-arrestin2.2.删除.
主要成果:
- 从应激细胞和小鼠中分离出AT1R丰富的外体,需要β-arrestin2进行贩运.
- 功能AT1Rs在体外通过外体转移,影响细胞伸展反应.
- 心肌细胞被确定为AT1R外体的来源在体内压力过载期间.
- 给予AT1R外基因组向了各种细胞类型,并恢复了淘汰小鼠的血管激素II反应.
结论:
- 心脏衍生AT1R丰富的外体在细胞应激下释放,以调节血管反应.
- 循环外因子体代表了功能性G蛋白结合受体的重要储备,包括AT1R.
- 这一发现扩大了对心血管调节中的受体贩运和细胞间通信的理解.
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