A New Conserved Player in Lymphatic Morphogenesis.

Abstract

The lymphatic system comprises a network of interconnected and blind-ended vessels whose central function is to maintain fluid homeostasis.1 Similar to the vessels of the circulatory system, the lymphatic system consists of a hierarchical network of small and large caliber vessels, which function together to allow fluid drainage. Lymphatic capillaries are lined by endothelial cells that are highly discontinuous, making them permeable to surrounding fluid to facilitate resorption. By contrast, larger lymphatic collecting ducts possess a thin smooth muscle layer and valves to promote unidirectional transport of fluid toward connection points with the circulatory system at the subclavian veins. In addition to fluid homeostasis, the lymphatic system and the constituent lymph nodes are a portal for lymphocytes, as well as antigen-presenting cells, while also functioning in lipid absorption in the digestive system.1 Given their wide-ranging importance in these normal physiological processes, it is not surprising that the lymphatic system is implicated in several pathological conditions. Indeed, inflammation is intimately associated with lymphatic function and is a central cause of lymphedema in a wide range of acquired and congenital diseases.1 Notably, congenital forms of lymphedema are associated with mutations in several genes important for lymphatic vessel formation, including those encoding the receptor tyrosine kinase FLT4 and its ligand, VEGFC.2 Articles, see p 1263 and 1276 The lymphatic system is also essential for cardiac homeostasis and has been increasingly implicated in related diseases. Importantly, lymphatic vessels can play a central role to facilitate repair of cardiac tissue after myocardial infarction.3 Indeed, injection of VEGFC after myocardial infarction can lead to sustained improvement in cardiac function, including increased ejection fraction, and reduction in both end-systolic volume and hypertrophy. In these cases, the presence of additional lymphatic vessels induced by VEGFC is thought to better resolve post-myocardial infarction edema …