Lymphatic versus blood vascular endothelial growth factors and receptors in humans

Three different growth factor systems have been described acting via endoth elial cell-specific receptor tyrosine kinases (RTKs). These are vascular en dothelial growth factors (VEGFs), angiopoietins, and ephrins. Recent studie s on gene targeting suggest that they play critical roles in embryonic deve lopment and contribute to the integrity and responses to environmental fact ors in the adult vasculature. Coagulation, inflammation, immune response re gulation, vascular tone, stromal component synthesis, and angiogenesis are all dependent on the physiological and pathological events that affect endo thelial cells in the heart, arteries, veins, and lymphatic vessels. Angioge nesis, the formation of new blood vessels from preexisting ones, takes plac e in adults only during hormonal control of female reproduction. All other activation of angiogenesis in adulthood occurs in response to injury or pat hological processes such as tumorigenesis, diabetes, or inflammatory condit ions. Insufficient growth of collateral vessels is a major problem in ather osclerotic cardiovascular disease. Controlled stimulation of angiogenesis w ould be of therapeutic value. Lymphangiogenesis, the mechanisms involved in the development of lymphatic vessels, was studied intensively nearly a cen tury ago, although since then it has been neglected, perhaps because, unlik e the disorders of blood vessels, those of the lymphatic vessels are seldom life-threatening. Interrupting this one-way system can cause severe disord ers, including liver dysfunction, genetic disease (e.g., Milroys disease), and degenerative disease (e.g., primary lymphangiosclerosis). Recently, nov el growth factors, receptors, cell surface proteins, and transcription fact ors have been found which play a role in the lymphatic endothelium. These a re VEGF-C, VEGF-D, VEGFR-3, LYVE-1, podoplanin, and Prox-1. Until recently lymphatic vessels have been difficult to study due to a lack of appropriate tools. Monoclonal antibodies raised against VEGFR-3 and against its ligand s, VEGF-C and VEGF-D, have offered an insight into expression studies in ti ssues. In this review, we summarize the recent data on VEGFs in the human v asculature. (C) 2001 Wiley-Liss, Inc.