Apelin signaling: new G protein-coupled receptor pathway in lymphatic vascular development.

The identification of novel factors that orchestrate the development, growth, and function of the lymphatic vascular system is a relatively new and coveted goal in the broad field of vascular biology. With the increased incidence of lymphedema and the recent recognition of the important roles that lymphatic vessels play in cancer, obesity, and metabolic disorders, there is a strong motivation to identify factors that could serve as pharmacological targets for the therapeutic modulation of lymphatic vessel growth and function.1 Because G protein–coupled receptors constitute the largest proportion of targets for prescribed pharmaceuticals, there is intense interest in revealing novel receptor pathways that could be targeted with highly specific agonists and antagonists.2 In this issue of Arteriosclerosis, Thrombosis, and Vascular Biology , Kim et al3 discover a new player in lymphatic vessels: Apelin signaling—a broadly expressed and multifunctional G protein–coupled receptors pathway that is part of the broader family of adipocytokine signaling.4,5 See accompanying article on page 338 Much of our knowledge on lymphatic vessel growth has come from developmental studies, whereby the establishment of lymphatic progenitor fate, migration, proliferation, and maturation can be elegantly teased apart using genetic approaches in mice and aquatic animal model systems.6,7 Lymphatic progenitors arise from venous endothelial cells, and the process of lymphatic endothelial cell migration away from parental veins can be stereotypically visualized and quantitated in zebrafish. Therefore, identifying key growth factors that are spatiotemporally expressed during this critical point of lymphatic vessel formation provides a strong foundation for the elucidation of new players. This pattern of highly restricted expression is precisely what led Kim et al to explore the possible functions of Apelin signaling in lymphatic development. Previous studies had shown that although the expression of Apelin receptors was broad during early zebrafish development, …