Mitochondrial respiration as a regulator of lymphatic cell fate and therapeutic lymphangiogenesis

摘要 血管内皮细胞(EC)代谢已成为血液和淋巴管的重要驱动力和调节器 血管发育，以及抗血管生成治疗的替代方法。事实证明， 新陈代谢不仅对EC的功能至关重要，而且对控制(淋巴)血管生成的不同步骤也是至关重要的。 进程。淋巴管表现出显著的可塑性和异质性，反映了它们的功能 控制组织微环境的专门化。我们最近的发现表明，通过感知淋巴 内皮细胞分化状态与微环境代谢条件、线粒体 复合体III调节LEC在胚胎发育过程中命运的指定和维持。类似于什么 显示为血液内皮细胞，很可能在不同的病理条件下，线粒体呼吸 对淋巴管的生长和扩张(淋巴管生成)也是必需的。我们认为线粒体 呼吸感知和调节晶状体上皮细胞的代谢状态是发育和发育过程中的关键步骤 疾病促进淋巴管生成，我们将在小鼠心脏损伤模型和 诱发急性和慢性胰腺炎。

Summary Endothelial cell (EC) metabolism has emerged as an essential driver and regulator of blood and lymphatic vessel development, as well as an alternative approach in anti-angiogenic therapy. It has been shown that metabolism is not only vital to EC function, but also to controlling different steps of the (lymph)-angiogenic process. Lymphatic vessels show remarkable plasticity and heterogeneity, reflecting their functional specialization to control the tissue microenvironment. Our recent findings revealed that by sensing the lymphatic endothelial cell (LEC) differentiation status and microenvironmental metabolic conditions, mitochondrial complex III regulates LEC fate specification and maintenance during embryonic development. Similar to what was shown for blood endothelial cells, most likely in different pathological conditions, mitochondrial respiration is also required for the growth and expansion (lymphangiogenesis) of lymphatics. We argue that mitochondrial respiration sensing and regulation of the metabolic status of LECs is a critical step during developmental and disease-promoted lymphangiogenesis, and we will evaluate this proposal in mouse models of cardiac injury and induced acute and chronic pancreatitis.