Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts
Vascular endothelial growth factor-A (VEGF) is one of the most important regulators of physiological and pathological angiogenesis, as demonstrated by genetic studies in which deletion of a single VEGF allele resulted in embryonic lethality caused by defective blood vessel formation. VEGF is an endothelial cell (EC) mitogen that serves as a mediator of angiogenesis and vessel permeability. As such, VEGF is essential for tumor growth and angiogenesis and is involved in ocular neovascularization characteristic of diabetic retinopathy and retinopathy of prematurity. VEGF belongs to a family of growth factors that includes VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-E, and placental growth factor (plGF). This chapter focuses on isoforms of VEGF-A resulting from alternative splicing. Therefore, throughout the text, VEGF-A will be referred to as VEGF.
VEGF is active as a homodimer by binding two receptor tyrosine kinases: VEGF receptor-1 (VEGFR1; Flt-1) and VEGF receptor-2 (VEGFR2; Fkl-1; KDR). VEGFR2 is primarily associated with the mitogenic and angiogenic activities of VEGF, whereas VEGFR1 is thought to be a reservoir for VEGF in solution, thereby regulating its availability. VEGF activity is regulated on many levels, including tran-scriptionally by cytokines and oxygen tension, and by alternative splicing of the VEGF gene to produce multiple isoforms that differ in their bioavailability and bioactivity. Increasing evidence suggests that VEGF isoform levels may be a major mechanism by which VEGF activity can be regulated physiologically and pathologically.
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This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.