糖酵解和线粒体呼吸作用在血管生成过程中内皮尖端细胞的形成和功能中的作用。,Scientific Reports

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糖酵解和线粒体呼吸作用在血管生成过程中内皮尖端细胞的形成和功能中的作用。
Scientific Reports ( IF 3.8 ) Pub Date : 2019-08-30 , DOI: 10.1038/s41598-019-48676-2
Bahar Yetkin-Arik _{1,

2} , Ilse M C Vogels _{1,

2} , Patrycja Nowak-Sliwinska ₃ , Andrea Weiss ₃ , Riekelt H Houtkooper ₄ , Cornelis J F Van Noorden _{2,

5} , Ingeborg Klaassen _{1,

2} , Reinier O Schlingemann _{1,

6}

Affiliation

在萌芽的血管生成过程中，单个的内皮尖端细胞从预先存在的血管网络中生长出来，并引导跟随并增殖的茎细胞形成新的血管。代谢途径（例如糖酵解和线粒体呼吸）是产生能量的5'-三磷酸腺苷（ATP）的主要来源，在血管生成过程中这些类型的内皮细胞（EC）中被不同地激活。因此，我们在尖细胞和非尖细胞人脐静脉内皮细胞中更详细地研究了血管生成过程中的能量代谢。小分子干扰RNA被用来抑制糖酵解酶PFKFB3或LDHA和线粒体酶PDHA1的转录，以测试这些特定途径的抑制作用在体外和体内是否影响末端细胞分化和发芽血管生成。我们显示糖酵解对于尖端细胞分化是必不可少的，而糖酵解和线粒体呼吸都发生在非尖端细胞的增殖过程中以及在体外和体内萌发的血管生成过程中。最后，我们证明抑制线粒体呼吸会通过增加糖酵解作用而导致EC代谢适应，反之亦然。总之，我们的研究表明，不同的代谢途径在产生ATP的过程中具有复杂而灵活的作用，从而在发芽血管生成过程中调节尖端细胞和非尖端细胞的分化和发挥功能。我们证明抑制线粒体呼吸会通过增加糖酵解作用而导致EC代谢适应，反之亦然。总之，我们的研究表明，不同的代谢途径在产生ATP的过程中具有复杂而灵活的作用，从而在发芽血管生成过程中调节尖端细胞和非尖端细胞的分化和发挥功能。我们证明抑制线粒体呼吸会通过增加糖酵解作用而导致EC代谢适应，反之亦然。总之，我们的研究表明，不同的代谢途径在产生ATP的过程中具有复杂而灵活的作用，从而在发芽血管生成过程中调节尖端细胞和非尖端细胞的分化和发挥功能。

"点击查看英文标题和摘要"

The role of glycolysis and mitochondrial respiration in the formation and functioning of endothelial tip cells during angiogenesis.

During sprouting angiogenesis, an individual endothelial tip cell grows out from a pre-existing vascular network and guides following and proliferating stalk cells to form a new vessel. Metabolic pathways such as glycolysis and mitochondrial respiration as the major sources of adenosine 5'-triphosphate (ATP) for energy production are differentially activated in these types of endothelial cells (ECs) during angiogenesis. Therefore, we studied energy metabolism during angiogenesis in more detail in tip cell and non-tip cell human umbilical vein ECs. Small interfering RNA was used to inhibit transcription of glycolytic enzymes PFKFB3 or LDHA and mitochondrial enzyme PDHA1 to test whether inhibition of these specific pathways affects tip cell differentiation and sprouting angiogenesis in vitro and in vivo. We show that glycolysis is essential for tip cell differentiation, whereas both glycolysis and mitochondrial respiration occur during proliferation of non-tip cells and in sprouting angiogenesis in vitro and in vivo. Finally, we demonstrate that inhibition of mitochondrial respiration causes adaptation of EC metabolism by increasing glycolysis and vice versa. In conclusion, our studies show a complex but flexible role of the different metabolic pathways to produce ATP in the regulation of tip cell and non-tip cell differentiation and functioning during sprouting angiogenesis.

更新日期：2019-08-30

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