Microvascular patterning is controlled by fine-tuning the Akt signal
Microvascular patterning is controlled by fine-tuning the Akt signal
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DOI：
10.1073/pnas.0403198102
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发表时间：
2005-01-04
影响因子：
11.1
通讯作者：
Benjamin, LE
中科院分区：
文献类型：
--
作者：
Sun, JF;Phung, T;Benjamin, LE
我们研究了Akt在血管发育和重塑过程中的功能，通过使用显性活性myrAkt的诱导内皮细胞特异性驱动程序。我们发现，持续的信号在过度表达myrAkt导致胚胎死亡，水肿和血管畸形。除了形态学畸形外，血管表型与重塑失败一致，因此正常模式和血管层次结构受到干扰。在重塑阶段对充分研究的视网膜血管系统的检查显示，myrAkt的瞬时表达能够改变对氧诱导的重塑的正常反应，而不引起血管畸形。这些发现表明，生理水平的Akt信号调节微血管重塑和支持的假设，虽然Akt可能是血管生长和稳态所需的，适当的下调也是正常的血管模式的一个重要方面。
We investigated the functions of Akt during vascular development and remodeling by using an inducible endothelial cell-specific driver of the dominant-active myrAkt. We found that sustained signaling in response to overexpression of myrAkt led to embryonic lethality, edema, and vascular malformations. In addition to the morphological malformations, the vascular phenotype was consistent with a failure in remodeling, such that the normal patterning and vessel hierarchy was disturbed. Examination of the well studied retinal vasculature during the remodeling phases revealed that transient expression of myrAkt was capable of altering the normal response to oxygen-induced remodeling without causing vascular malformations. These findings suggest that physiological levels of Akt signaling modulated microvascular remodeling and support the hypothesis that, although Akt may be required for vascular growth and homeostasis, appropriate downregulation is also an essential aspect of normal vascular patterning.