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内皮Rho激酶控制血管完整性和血管生成

Martin Lange^1,2, Caitlin Francis^1,2, Jessica Furtado^1,2

¹Cardiovascular Research Center, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA.

bioRxiv : the preprint server for biology

|November 28, 2024

概括

内皮Rho激酶1和2 (ROCK1/2) 对于血管完整性和血管生成至关重要. 这些激酶的损失会导致致命的出血,强调在疾病中使用ROCK抑制剂时需要谨慎.

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
分子生物学分子生物学

背景情况:

罗基因酶1和2 (ROCK1/2) 是活性蛋白细胞骨动态的关键调节者.
ROCK1/2对心血管健康和疾病至关重要,药物抑制在各种模型中显示出好处.
内皮内皮ROCK信号的特定作用在体内仍然在很大程度上是未知的.

研究的目的:

在体内研究内皮细胞特异性ROCK1和ROCK2缺乏的后果.
阐明内皮ROCK信号在维持血管完整性和血管生成中的作用.

主要方法:

产生他莫西芬诱导性内皮细胞特异性ROCK1和ROCK2功能丧失的小鼠模型.
利用细胞,生化和分子生物学方法来分析血管缺陷.
进行了体外3D内皮发芽试验,以评估血管生成和光膜形成.

主要成果:

产后或成人内皮ROCK1/2的损失在一周内是致命的,原因是多器官出血和血管完整性的损失.
内皮细胞显示出有缺陷的活性蛋白聚合,焦点粘附形成受损,并破坏了结合完整性.
血管新生受到了干扰,有缺陷的乙聚合,光膜形成和细胞极化,特别是在ROCK2缺乏的情况下.

结论:

内皮ROCK1和ROCK2对于维持血管完整性,正确的血管生成和光膜形成至关重要.
一个单一的ROCK2等位基因足以维持血管生长和完整性.
这些发现需要仔细考虑在疾病环境中使用ROCK抑制剂.

关键词:

在Rock1上,你会看到Rock1.在Rock2上,我一直在努力.细胞结节细胞结节细胞骨架细胞骨架它们是内皮细胞的内皮细胞.焦点粘附的焦点粘附.发生出血发生出血

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