The molecular mechanisms that create, separate, and regulate the lymphatic and blood vascular systems have important implications for our understanding of the development of the vascular system, events in some forms of vascular disease, and possible new avenues for therapy for several diseases. Specific and selective markers (LYVE-1, VEGF-R3, Prox-1) now exist that can distinguish LEC from BEC differentiation at several levels, particularly the genetic and molecular levels and permit the separation of these different populations for examination of their properties. Several of these new structural and functional LEC markers permit selective targeting of LECs, and examination of their unique roles in development and their contributions to several important pathologies. These studies on LEC markers have in only a few years already provided remarkably important new evidence for the roles of lymphatics in several diseases including cancer, lymphedema, wound healing, and inflammation. These results promise to provide additional information on the roles of lymphatics in many other diseases of the immune system, development, and iatrogenic complications. Most importantly, these markers not only provide prognostic signs of specific features of disease, but also provide new mechanisms for disease processes, and consequently important new targets for prophylactic and therapeutic intervention.
Chemokines: Soluble polypeptide factors secreted by immune system cells that stimulate some activity of other cells. Chemokines are often chemoattractants and act as tertiary messengers between cells.
Lymphedema: Swelling in the extremities caused by interstitial fluid buildup in tissues due to congenital malformation of lymphatics (primary) or surgical/traumatic (secondary) loss of lymphatic drainage (e.g., when nodes are removed or blocked).
VEGFs: A family of structurally related proteins that stimulate growth of blood and lymphatic endothelial cells and several other cell types. VEGF actions are stimulated through binding to VEGF receptors VEGFRs 1, 2, and 3. Placental growth factor (PlGF) and VEGF-B bind primarily to VEGFR-1. PlGF modulates angiogenesis and may participate in inflammation. VEGF-C and VEGF-D bind primarily to VEGFR-3 and stimulate lym-phangiogenesis rather than angiogenesis.
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Dr. Alexander has been a member of the department of Molecular and Cellular Physiology in Shreveport, LA. since 1993 and the codirector of the cell biology core, and the director of research for the department of Gas-troenterology. His laboratory primarily focuses on the roles of endothelial cells in chronic inflammation, cancer, and cardiovascular disease. The NIH has supported his work since 1993.
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