Teuwen Laure-Anne, Geldhof Vincent, Carmeliet Peter
Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, KU Leuven, Leuven B-3000, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, VIB Center for Cancer Biology, VIB, Leuven B-3000, Belgium; Translational Cancer Research Unit, GZA Hospitals Sint-Augustinus, Wilrijk B-2610, Belgium and Center for Oncological Research University of Antwerp, Antwerp B-2610, Belgium.
Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, KU Leuven, Leuven B-3000, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, VIB Center for Cancer Biology, VIB, Leuven B-3000, Belgium.
Dev Biol. 2019 Mar 1;447(1):90-102. doi: 10.1016/j.ydbio.2017.12.001. Epub 2017 Dec 7.
Recently, endothelial cell metabolism has emerged as an essential driver and regulator of both blood and lymph vessel development. Evidence rapidly builds that metabolism is not only necessary for endothelial cell function, but moreover controls several aspects of the (lymph)-angiogenic process. So far, the best-characterized metabolic pathways to have an impact on angiogenesis are glycolysis, fatty acid oxidation and glutamine metabolism. Glycolysis regulates tip cell behavior by providing ATP, fatty acid oxidation controls stalk cell proliferation by producing nucleotide biomass, and glutamine metabolism is critical for tip and stalk cell dynamics by supporting Krebs cycle anaplerosis, protein production and redox homeostasis, and links to asparagine metabolism. During lymphangiogenesis, glycolysis and fatty acid oxidation are key metabolic pathways. Glycolysis provides energy for growing lymph vessels, while fatty acid oxidation is a critical metabolic regulator of lymphangiogenesis, in part by promoting nucleotide synthesis as well as by mediating epigenetic changes of histone acetylation, which promotes transcription of key lymphatic genes, and hence venous-to-lymphatic endothelial cell differentiation. On the whole, increasing knowledge on the metabolic landscape of endothelial cells offers a fresh impetus to future treatment possibilities of vascular related diseases.
最近，内皮细胞代谢已成为血管和淋巴管发育的重要驱动因素和调节因子。越来越多的证据表明，代谢不仅是内皮细胞功能所必需的，而且还控制着（淋巴）血管生成过程的多个方面。到目前为止，对血管生成有影响的最具特征的代谢途径是糖酵解、脂肪酸氧化和谷氨酰胺代谢。糖酵解通过提供ATP来调节顶端细胞行为，脂肪酸氧化通过产生核苷酸生物量来控制柄细胞增殖，而谷氨酰胺代谢对于顶端和柄细胞的动态变化至关重要，它支持三羧酸循环的回补反应、蛋白质合成和氧化还原稳态，并与天冬酰胺代谢相关。在淋巴管生成过程中，糖酵解和脂肪酸氧化是关键的代谢途径。糖酵解为生长中的淋巴管提供能量，而脂肪酸氧化是淋巴管生成的关键代谢调节因子，部分原因是通过促进核苷酸合成以及介导组蛋白乙酰化的表观遗传变化，从而促进关键淋巴管基因的转录，进而促进静脉内皮细胞向淋巴管内皮细胞的分化。总体而言，对内皮细胞代谢格局的认识不断增加为血管相关疾病的未来治疗可能性提供了新的动力。
