Cardiac lymphatics are heterogeneous in origin and respond to injury.

Abstract

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.

• Authors: Linda Klotz, Sophie Norman, Joaquim Miguel Vieira, Megan Masters, Mala Rohling, Karina N Dubé, Sveva Bollini, Fumio Matsuzaki, Carolyn A Carr, Paul R Riley
• Journal: Nature (Nature) Vol. 522 Issue 7554 Pg. 62-7 (Jun 04 2015) ISSN: 1476-4687 [Electronic] England
• PMID: 25992544 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Homeodomain Proteins
• Proto-Oncogene Proteins c-vav
• Tumor Suppressor Proteins
• Vascular Endothelial Growth Factor C
• Vav1 protein, mouse
• prospero-related homeobox 1 protein
• Receptor, Macrophage Colony-Stimulating Factor
• Receptor, Platelet-Derived Growth Factor beta
• Receptor, TIE-2
• Tek protein, mouse

Topics

• 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)