Zhao Zimin, Li Peilin, Liu Zhong, Cui Yonghao, Yao Zixuan, Chen Weijian, Wang Mengqin, Yu Chengyuan, Xia Song, Sun Yuguang, Zhang Nengwei, Shen Wenbin
Department of Lymphatic Surgery, Capital Medical University Affiliated Beijing Shijitan Hospital; Clinical Center for Lymphatic Disorders, CMU, China.
Center for Obesity and Metabolic Disease, Capital Medical University Affiliated Beijing Shijitan Hospital, Beijing, China.
Int J Biol Macromol. 2025 Mar;294:139038. doi: 10.1016/j.ijbiomac.2024.139038. Epub 2024 Dec 19.
This study offers new insights into the dual role of secretory phospholipase A2 (sPLA2) in lymphedema, highlighting its impact on lymphatic endothelial cell (LEC) functionality. Through transcriptomic analyses and co-culture experiments, we observed that sPLA2 has both protective and detrimental effects on human LECs (HLECs), mediated by macrophage activation. Our findings reveal that while low levels of sPLA2 promote LEC health, excessive sPLA2 leads to dysfunction, emphasizing the significance of the sPLA2/PLA2R axis and arachidonic acid metabolism (AA) in lymphedema pathology. The study suggests targeting sPLA2 and its downstream pathways as a novel therapeutic strategy for lymphedema, aiming to mitigate its progression by safeguarding HLEC integrity. This research underscores the importance of balanced sPLA2 activity in maintaining lymphatic vessel health and presents a new avenue for lymphedema management and treatment.
本研究为分泌型磷脂酶A2（sPLA2）在淋巴水肿中的双重作用提供了新的见解，突出了其对淋巴管内皮细胞（LEC）功能的影响。通过转录组分析和共培养实验，我们观察到sPLA2对人淋巴管内皮细胞（HLEC）具有保护和有害作用，这是由巨噬细胞激活介导的。我们的研究结果表明，虽然低水平的sPLA2促进LEC健康，但过量的sPLA2会导致功能障碍，强调了sPLA2/PLA2R轴和花生四烯酸代谢（AA）在淋巴水肿病理中的重要性。该研究建议将sPLA2及其下游途径作为淋巴水肿的一种新型治疗策略，旨在通过保护HLEC完整性来减轻其进展。这项研究强调了平衡sPLA2活性在维持淋巴管健康中的重要性，并为淋巴水肿的管理和治疗提供了一条新途径。
