Endothelial cells (ECs) are more than inert blood vessel lining material. Instead, they are active players in the formation of new blood vessels (angiogenesis) both in health and (life-threatening) diseases. Recently, a new concept arose by which EC metabolism drives angiogenesis in parallel to well-established angiogenic growth factors (e.g., vascular endothelial growth factor). 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3-driven glycolysis generates energy to sustain competitive behavior of the ECs at the tip of a growing vessel sprout, whereas carnitine palmitoyltransferase 1a-controlled fatty acid oxidation regulates nucleotide synthesis and proliferation of ECs in the stalk of the sprout. To maintain vascular homeostasis, ECs rely on an intricate metabolic wiring characterized by intracellular compartmentalization, use metabolites for epigenetic regulation of EC subtype differentiation, crosstalk through metabolite release with other cell types, and exhibit EC subtype-specific metabolic traits. Importantly, maladaptation of EC metabolism contributes to vascular disorders, through EC dysfunction or excess angiogenesis, and presents new opportunities for anti-angiogenic strategies. Here we provide a comprehensive overview of established as well as newly uncovered aspects of EC metabolism.

中文翻译：

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内皮细胞代谢

内皮细胞 (EC) 不仅仅是惰性血管内壁材料。相反，它们是健康和（危及生命的）疾病中新血管形成（血管生成）的积极参与者。最近，出现了一个新概念，即 EC 代谢与成熟的血管生成生长因子（例如血管内皮生长因子）同时驱动血管生成。6-磷酸果糖-2-激酶/果糖-2,6-双磷酸酶-3 驱动的糖酵解产生能量以维持生长中的血管芽尖端 EC 的竞争行为，而肉碱棕榈酰转移酶 1a 控制的脂肪酸氧化调节核苷酸合成以及芽茎中 EC 的增殖。为了维持血管稳态，EC 依赖于以细胞内区室化为特征的复杂代谢线路，使用代谢物对 EC 亚型分化进行表观遗传调控，通过代谢物释放与其他细胞类型进行串扰，并表现出 EC 亚型特异性代谢特征。重要的是，EC 代谢的适应不良通过 EC 功能障碍或过度血管生成导致血管疾病，并为抗血管生成策略提供了新的机会。在这里，我们对 EC 代谢的已建立和新发现的方面进行了全面概述。