Endothelial-specific expression of caveolin-1 impairs microvascular permeability and angiogenesis
Endothelial-specific expression of caveolin-1 impairs microvascular permeability and angiogenesis
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DOI：
10.1073/pnas.0406092102
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发表时间：
2005-01-04
影响因子：
11.1
通讯作者：
Sessa, WC
中科院分区：
文献类型：
--
作者：
Bauer, PM;Yu, J;Sessa, WC
在完整的动物小窝和/或小窝蛋白的功能开始被探索。在这里，通过使用内皮细胞特异性转基因的小窝蛋白-1（Cav-1）的基因在小鼠中，我们显示的关键作用，Cav-1在几个出生后的血管范例。首先，增加Cav-1水平不会增加体内内皮细胞中的小窝数量。第二，尽管缺乏细胞器数量的定量变化，Cav-1的内皮特异性表达损害内皮一氧化氮合酶的激活，内皮屏障功能，和血管生成反应外源性VEGF和组织缺血。此外，VEGF介导的Akt及其底物内皮型一氧化氮合酶磷酸化在VEGF处理的Cav-1转基因小鼠中显著降低，与WT同窝小鼠相比。Cav-1表达对Akt-内皮型一氧化氮合酶途径的抑制作用是特异性的，因为与同窝出生的小鼠相比，Cav-1转基因小鼠中VEGF刺激的丝裂原活化蛋白激酶（ERK 1/2）磷酸化水平升高。这些数据强烈支持的想法，在体内，Cav-1可以调节信号转导通路独立的小窝生物发生的重要作用。
The functions of caveolae and/or caveolins in intact animals are beginning to be explored. Here, by using endothelial cell-specific transgenesis of the caveolin-1 (Cav-1) gene in mice, we show the critical role of Cav-1 in several postnatal vascular paradigms. First, increasing levels of Cav-1 do not increase caveolae number in the endothelium in vivo. Second, despite a lack of quantitative changes in organelle number, endothelial-specific expression of Cav-1 impairs endothelial nitric oxide synthase activation, endothelial barrier function, and angiogenic responses to exogenous VEGF and tissue ischemia. In addition, VEGF-mediated phosphorylation of Akt and its substrate, endothelial nitric oxide synthase, were significantly reduced in VEGF-treated Cav-1 transgenic mice, compared with WT littermates. The inhibitory effect of Cav-1 expression on the Akt-endothelial nitric oxide synthase pathway was specific because VEGF-stimulated phosphorylation of mitogen-activated protein kinase (ERK1/2) was elevated in the Cav-1 transgenics, compared with littermates. These data strongly support the idea that, in vivo, Cav-1 may modulate signaling pathways independent of its essential role in caveolae biogenesis.