Cardiac lymphatics are heterogeneous in origin and respond to injury

Article

关键词: VASCULAR ENDOTHELIAL-CELLS;    VESSEL DEVELOPMENT;    TRANSGENIC MICE;    PROX1;    VEGF;    LYMPHANGIOGENESIS;    PROGENITORS;    EXPRESSION;    LINEAGE;    HEART;   

DOI  :  10.1038/nature14483

来源: SCIE

【 摘 要 】

The lymphatic vasculature is a blind-ended network crucial for tissue-fluid homeostasis, immune surveillance and lipid absorption from the gut. Recent evidence has proposed an entirely venous-derived mammalian lymphatic system. By contrast, here we show that cardiac lymphatic vessels in mice have a heterogeneous cellular origin, whereby formation of at least part of the cardiac lymphatic network is independent of sprouting from veins. Multiple Cre-lox-based lineage tracing revealed a potential contribution from the putative haemogenic endothelium during development, and discrete lymphatic endothelial progenitor populations were confirmed by conditional knockout of Prox1 in Tie2(+) and Vav1(+) compartments. In the adult heart, myocardial infarction promoted a significant lymphangiogenic response, which was augmented by treatment with VEGF-C, resulting in improved cardiac function. These data prompt the re-evaluation of a century-long debate on the origin of lymphatic vessels and suggest that lymphangiogenesis may represent a therapeutic target to promote cardiac repair following injury.

【 授权许可】

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