NETosis 驱动高血压升高和高血压中的血管功能障碍
Jaya Krishnan1, Elizabeth M Hennen2, Mingfang Ao3
1Division of Clinical Pharmacology, Department of Medicine (J.K., A.K., T.A., N.d.l.V., D.M.P.), Vanderbilt University Medical Center, Nashville, TN.
中性细胞外细胞陷 (NETs) 通过引起内皮细胞功能障碍,导致高血压. 机械敏感通道TRPV4和内皮细胞伸展启动NETosis,而素基因组激素会恶化高血压.
科学领域:
- 心血管生物学 心血管生物学
- 免疫学 免疫学 免疫学
- 细胞生理学 细胞生理学
背景情况:
- 中性粒细胞外细胞陷 (NETs),包括DNA,酶和素基因组,在NETosis期间释放.
- 在高血压患者的大动脉和脏中发现了NET.
- 蛋白质-氨酸减小酶-4 (PAD4) 对于NETosis至关重要,而过渡受体潜在通道亚家族V成员4 (TRPV4) 是中性粒细胞中的机械敏感通道.
研究的目的:
- 调查NETosis在高血压中的作用.
- 为了确定NETosis是否有助于内皮细胞 (EC) 功能障碍.
- 探索TRPV4和EC stretch在启动NETosis中的参与.
主要方法:
- 使用了接受 angiotensin II (Ang II) 治疗的 NETosis 缺陷小鼠.
- 通过流式细胞计和免疫光学测量血压,血管反应性和NETosis.
- 在暴露于用TRPV4激动剂治疗的素化组合素H3和中性粒细胞后评估EC功能.
主要成果:
- 在Padi4小鼠中,高血压降低,大动脉炎症降低,血管放松改善.
- 与中性粒细胞共同培养的高血压延伸EC增加了NETosis和素化组合素H3的积累.
- 素基因组H3损害了依赖EC的血管放松,TRPV4的激活增加了的流入和NETosis.
结论:
- NETosis 在高血压的发病过程中起作用.
- 内皮细胞伸展和TRPV4是NETosis的发起者.
- 在高血压中,素基因组驱动内皮细胞功能障碍.
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