Lymphatic versus blood vascular endothelial growth factors and receptors in humans.
Three different growth factor systems have been described acting via endothelial cell-specific receptor tyrosine kinases (RTKs). These are vascular endothelial growth factors (VEGFs), angiopoietins, and ephrins. Recent studies on gene targeting suggest that they play critical roles in embryonic development and contribute to the integrity and responses to environmental factors in the adult vasculature. Coagulation, inflammation, immune response regulation, vascular tone, stromal component synthesis, and angiogenesis are all dependent on the physiological and pathological events that affect endothelial cells in the heart, arteries, veins, and lymphatic vessels. Angiogenesis, the formation of new blood vessels from preexisting ones, takes place in adults only during hormonal control of female reproduction. All other activation of angiogenesis in adulthood occurs in response to injury or pathological processes such as tumorigenesis, diabetes, or inflammatory conditions. Insufficient growth of collateral vessels is a major problem in atherosclerotic cardiovascular disease. Controlled stimulation of angiogenesis would be of therapeutic value. Lymphangiogenesis, the mechanisms involved in the development of lymphatic vessels, was studied intensively nearly a century ago, although since then it has been neglected, perhaps because, unlike the disorders of blood vessels, those of the lymphatic vessels are seldom life-threatening. Interrupting this one-way system can cause severe disorders, including liver dysfunction, genetic disease (e.g., Milroys disease), and degenerative disease (e.g., primary lymphangiosclerosis). Recently, novel growth factors, receptors, cell surface proteins, and transcription factors have been found which play a role in the lymphatic endothelium. These are 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 ligands, VEGF-C and VEGF-D, have offered an insight into expression studies in tissues. In this review, we summarize the recent data on VEGFs in the human vasculature.
Partanen TA
,Paavonen K
《MICROSCOPY RESEARCH AND TECHNIQUE》
VEGFs, receptors and angiogenesis.
Angiogenesis, the formation of new blood vessels from pre--existing ones, is central for both normal development and homeostasis as well as in certain pathological conditions. The vascular endothelial growth factors (VEGFs) and their receptors are prime regulators of both physiological and pathological angiogenesis. The different VEGFs have overlapping but specific roles in controlling the growth of new blood vessels. The VEGF receptors transduce signals mediating endothelial cell proliferation, migration, organization into functional vessels and remodeling of the vessel network. In recent years, rapid progress has been made in understanding the receptor-ligand interactions that orchestrate the neovascularization process.
Veikkola T
,Alitalo K
《SEMINARS IN CANCER BIOLOGY》