Department of Medicine, Faculty of Medicine, Université de Montréal, Montreal, Canada.
Montreal Heart Institute, Montreal, Canada.
Commun Biol. 2024 Aug 11;7(1):975. doi: 10.1038/s42003-024-06675-8.
Lymphatic vessels are essential for preventing the accumulation of harmful components within peripheral tissues, including the artery wall. Various endogenous mechanisms maintain adequate lymphatic function throughout life, with platelets being essential for preserving lymphatic vessel integrity. However, since lymph lacks platelets, their impact on the lymphatic system has long been viewed as restricted to areas where lymphatics intersect with blood vessels. Nevertheless, platelets can also exert long range effects through the release of extracellular vesicles (EVs) upon activation. We observed that platelet EVs (PEVs) are present in lymph, a compartment to which they could transfer regulatory effects of platelets. Here, we report that PEVs in lymph exhibit a distinct signature enabling them to interact with lymphatic endothelial cells (LECs). In vitro experiments show that the internalization of PEVs by LECs maintains their functional integrity. Treatment with PEVs improves lymphatic contraction capacity in atherosclerosis-prone mice. We suggest that boosting lymphatic pumping with exogenous PEVs offers a novel therapeutic approach for chronic inflammatory diseases characterized by defective lymphatics.
淋巴管对于防止有害成分在周围组织（包括动脉壁）中积累至关重要。各种内源性机制可维持整个生命周期中的充分淋巴管功能，而血小板对于保持淋巴管完整性至关重要。然而，由于淋巴液中缺乏血小板，它们对淋巴管系统的影响长期以来一直被认为仅限于淋巴管与血管相交的区域。然而，血小板在激活时通过释放细胞外囊泡（EVs）也可以发挥远程效应。我们观察到血小板 EVs（PEVs）存在于淋巴中，它们可以将血小板的调节作用传递到这一部位。在这里，我们报告说，淋巴中的 PEVs 具有独特的特征，使它们能够与淋巴管内皮细胞（LECs）相互作用。体外实验表明，LECs 内化 PEVs 可维持其功能完整性。用 PEVs 处理可改善易患动脉粥样硬化的小鼠的淋巴管收缩能力。我们认为，用外源性 PEVs 增强淋巴泵功能为以淋巴管功能缺陷为特征的慢性炎症性疾病提供了一种新的治疗方法。
