在血管内皮中β位粉样蛋白前体蛋白分裂酶2的表达和功能
Livius V d'Uscio1,2, Tetiana Kovalenko3, Tongrong He1,2
1Department of Anesthesiology and Perioperative Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota, United States.
概括
在内皮细胞中的β位粉样蛋白前体蛋白分裂酶2 (BACE2) 缺乏,通过增加血管缩性前列腺体,损害了大动脉放松. 这项研究揭示了BACE2在调节血管功能和酸代谢中的作用.
科学领域:
- 血管生物学 血管生物学
- 酶的功能 酶的功能
- 内皮细胞生理学 内皮细胞生理学
背景情况:
- 在系统性动脉的血管内皮中,β位粉样蛋白前体蛋白分裂酶2 (BACE2) 的生理作用在很大程度上是未知的.
- BACE2蛋白主要局限于大动脉的内皮细胞内.
研究的目的:
- 为了研究BACE2在全身动脉内皮细胞中的功能.
- 阐明BACE2影响内皮功能和血管运动活动的机制.
主要方法:
- 产生有条件的他莫西芬诱导性内皮 BACE2 缺陷小鼠 (eBACE2-/-).
- 使用各种药理剂评估大动脉组织中依赖内皮和独立放松的评估.
- 通过Western blot,ELISA和实时PCR分析氧化合成酶 (NOS) 表达,循环核酸水平和前列腺素生产.
主要成果:
- BACE2的内皮缺失显著损害了对A23187的内皮依赖放松,而内皮独立放松没有受到影响.
- 在eBACE2-/- aortas.中观察到血管约束性前列腺体的产量增加,特别是血栓素A2和前列腺素F2α.
- 用血栓素A2受体对抗剂治疗改善了BACE2-缺乏小鼠中受损放松的情况.
结论:
- BACE2在控制内皮甲基酸代谢和维持正常血管运动功能方面发挥着至关重要的作用.
- 血管缩性前列腺体产生的增加有助于在缺少内皮BACE2.2的情况下观察到的内皮依赖放松功能受损.
- 这项研究揭示了BACE2在调节血管和前列腺蛋白合成方面的新功能.
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