淋巴管是机体循环、代谢和免疫系统的重要组成，且与多种疾病发生密切相关。既往研究以PROX1和VEGFRs为主，充分揭示了转录因子和信号通路在淋巴管形成中的重要性，而细胞能量代谢在其中发挥的作用仍未可知。我们的前期研究发现，膜通透性琥珀酸可以刺激内皮细胞线粒体复合物Ⅱ活性，促使其依赖于高水平氧化磷酸化供能。结合体内模型，我们发现这种细胞内琥珀酸的堆积可以显著刺激内皮细胞形成血管和淋巴管的能力。因此，我们提出假设，琥珀酸介导的线粒体能量代谢可以通过影响淋巴管内皮细胞（LECs）结构和功能调控淋巴管发育和病理形成。为此，本项目将以琥珀酸调控的能量代谢与LECs功能的交互调控为基础，确定琥珀酸代谢异常与线粒体能量代谢改变在淋巴管发育和形成中的作用，探究琥珀酸代谢在淋巴管异常相关疾病中的应用潜能，形成治疗新策略。

Lymphatic vessels are very important for the physiological homeostasis of circulation, metabolism and immune system, and are involved in many pathological processes. Previous studies focused on PROX1 and VEGFRs have already discovered the key role of transcription factors and signaling pathways in lymphangiogenesis, while the regulatory effects of cellular energy metabolism remain largely unknown. Here, we found that the permeable succinate could enhance the activity of mitochondrial complex Ⅱ in endothelial cells and increased the utilization of oxidative phosphorylation for energy production. Through in vivo studies, we found that the accumulation of intracellular succinate could significantly increase the ability of endothelial cells to form blood vessels and lymphatic vessels. Therefore, we hypothesized that succinate-mediated mitochondrial energy metabolism could control the process of lymphangiogenesis by modulating the structure and function of lymphatic endothelial cells (LECs). Thus, we will investigate the interaction between succinate-mediated energy metabolism and LECs function, the role of changes in succinate and energy metabolism in the development and pathogenesis of lymphatic vessels, and the application potential of succinate-mediated metabolism in diseases treatment. We believe that the completion of this project will expand our understanding of lymphangiogenic regulation and develop new therapeutic strategies.