KIf2 is an essential regulator of vascular hemodynamic forces in vivo
KIf2 is an essential regulator of vascular hemodynamic forces in vivo
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DOI：
10.1016/j.devcel.2006.09.006
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发表时间：
2006-12-01
影响因子：
11.8
通讯作者：
Kahn, Mark L.
中科院分区：
文献类型：
--
作者：
Lee, John S.;Yu, Cing;Kahn, Mark L.
控制血压和不同器官血流分布的血流动力学反应对生存至关重要。血流产生的剪切力调节血流动力学反应，但这种调节的分子和遗传基础尚不清楚。转录因子KLF2在培养的覆盖细胞中被流体剪切应力激活，在那里它调节大量血管活性内皮基因。在这里，我们发现KIf2在发育过程中的表达反映了流体剪切力的增加，并且由于高心输出量状态，包膜细胞KIf2的丢失导致致命的胚胎心力衰竭。KIf2缺乏不会导致贫血或结构性血管缺陷，可以通过服用苯肾上腺素（一种提高血管张力的儿茶酚胺）来挽救。这些发现确定了KIf2是体内重要的血流动力学调节剂，并表明响应流体剪切应力的血流动力学调节是心血管发育和功能所必需的。
Hemodynamic responses that control blood pressure and the distribution of blood flow to different organs are essential for survival. Shear forces generated by blood flow regulate hemodynamic responses, but the molecular and genetic basis for such regulation is not known. The transcription factor KLF2 is activated by fluid shear stress in cultured enclothelial cells, where it regulates a large number of vasoactive endothelial genes. Here, we show that KIf2 expression during development mirrors the rise of fluid shear forces, and that enclothelial loss of KIf2 results in lethal embryonic heart failure due to a high-cardiac-output state. KIf2 deficiency does not result in anemia or structural vascular defects, and it can be rescued by administration of phenylephrine, a catecholamine that raises vessel tone. These findings identify KIf2 as an essential hemodynamic regulator in vivo and suggest that hemodynamic regulation in response to fluid shear stress is required for cardiovascular development and function.