Publication Date:
2015-05-21
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4458138/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4458138/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Klotz, Linda -- Norman, Sophie -- Vieira, Joaquim Miguel -- Masters, Megan -- Rohling, Mala -- Dube, Karina N -- Bollini, Sveva -- Matsuzaki, Fumio -- Carr, Carolyn A -- Riley, Paul R -- CH/11/1/28798/British Heart Foundation/United Kingdom -- PG/13/34/30216/British Heart Foundation/United Kingdom -- RG/08/003/25264/British Heart Foundation/United Kingdom -- RM/13/3/30159/British Heart Foundation/United Kingdom -- British Heart Foundation/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2015 Jun 4;522(7554):62-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25992544" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Cell Lineage
;
Endothelial Cells/cytology/metabolism
;
Female
;
Heart/physiology/physiopathology
;
Homeodomain Proteins/metabolism
;
*Lymphangiogenesis
;
Lymphatic Vessels/*cytology/*injuries/metabolism
;
Male
;
Mice
;
Mice, Inbred C57BL
;
Myocardial Infarction/metabolism/physiopathology
;
Myocardium/*cytology/metabolism
;
Proto-Oncogene Proteins c-vav/metabolism
;
Receptor, Macrophage Colony-Stimulating Factor/metabolism
;
Receptor, Platelet-Derived Growth Factor beta/metabolism
;
Receptor, TIE-2/metabolism
;
Spatio-Temporal Analysis
;
Tumor Suppressor Proteins/deficiency/metabolism
;
Vascular Endothelial Growth Factor C/metabolism
;
Veins/cytology
;
Yolk Sac/cytology
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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