Journal
NATURE
Volume 522, Issue 7554, Pages 62-U126Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nature14483
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Funding
- Wellcome Trust
- EU FP7 Marie Curie ITN (CardioNet)
- British Heart Foundation
- British Heart Foundation [RG/13/9/30269, RG/08/003/25264, PG/13/34/30216] Funding Source: researchfish
- Grants-in-Aid for Scientific Research [24113006] Funding Source: KAKEN
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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.
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