Role of VEGF/VEGFR and angiopoietin/tie system in blood and lymphatic vessels remodeling

Abstract

In the multicellular organisms, highly-branched blood and lymphatic vascular networks are responsible for transporting gases, nutrients, signaling molecules and circulating cells between tissues and organs through the body. The vascular networks are formed by endothelial cells which are tightly regulated to maintain the homeostasis in the organism via various signaling pathways. Occasionally, dysfunction in the vascular networks is associated with many diseases such as cancer and cardiovascular diseases. In early embryonic development, endothelial cells aggregate to form primitive blood vessels (vasculogenesis). Once the blood circulation becomes established, initial vascular plexus develops into a complex and functional vascular structure through various vascular remodeling processes such as endothelial cell sprouting, pruning, and vascular branching (angiogenesis). Vascular endothelial growth factor (VEGF)/VEGF receptor and angiopoietin/Tie receptor system have been identified to be endothelial cell-specific and essential for the formation and maintenance of vascular network not merely in embryonic development but also in the adult life. Here, I divided this thesis into three chapters as follows: the development of lymphatic vessels in the mouse intestine (part I), role of VEGF-C,D/VEGFR-3 system in inflammation-induced lymphangiogenesis (part II), and role of angiopoietins/Tie2 system in angiogenesis and lymphangiogenesis (part III). $\Bf{Part I. Abstract}$ Lymphatic vessels in the small intestine serve as essential conduits for the absorption and transport of lipids from the intestine to the thoracic duct. Although the morphology and function of the intestinal lymphatic vasculature are well known, little is known about the embryonic development of these vessels. In this study, I examined development of lymphatic and blood vasculatures in the intestinal tube during mouse embryonic development by immunostaining with recently discovered molecular marker...