Vascular endothelial growth factor (VEGF) is an important signaling protein involved in both vasculogenesis (the de novo formation of the embryonic circulatory system) and angiogenesis (the growth of blood vessels from pre-existing vasculature). As its name implies, VEGF activity is restricted mainly to cells of the vascular endothelium, although it does have effects on a limited number of other cell types (e.g. stimulation monocyte/macrophage migration). In vitro, VEGF has been shown to stimulate endothelial cell mitogenesis and cell migration. VEGF also enhances microvascular permeability and is sometimes referred to as vascular permeability factor. Hugo is a masculine name. ... The Entrez logo The Entrez Global Query Cross-Database Search System allows access to databases at the National Center for Biotechnology Information (NCBI) website. ... The Mendelian Inheritance in Man project is a database that catalogues all the known diseases with a genetic component, and - when possible - links them to the relevant genes in the human genome. ... The National Center for Biotechnology Information (NCBI) is part of the US National Library of Medicine (NLM), which is a branch of the US National Institutes of Health. ... Swiss-Prot is a curated biological database of protein sequences created in 1986 by Amos Bairoch during his PhD and developed by the Swiss Institute of Bioinformatics and the European Bioinformatics Institute. ... In biology and evolutionary computation, a locus is the position of a gene (or other significant sequence) on a chromosome. ... Chromosome 6 is one of the 23 pairs of chromosomes in humans. ... A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... Vasculogenesis is the process of blood vessel formation occuring by a de novo production of endothelial cells. ... In law, the expression trial de novo literally means new trial. It is most often used in certain legal systems that provide for one form of trial, then another if a party remains unsatisfied with the decision. ... Human circulatory system. ... Angiogenesis is the physiological process involving the growth of new blood vessels from pre-existing vessels. ... The endothelium is the layer of thin, flat cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. ... Monocyte A monocyte is a leukocyte, part of the human bodys immune system that protect against blood-borne pathogens and move quickly to sites of infection in the tissues. ... A macrophage of a mouse stretching its arms to engulf two particles, possibly pathogens Macrophages (Greek: big eaters, makros = long, phagein = eat) are white blood cells, more specifically phagocytes, acting in the nonspecific defense as well as the specific defense system of vertebrate animals. ... Light micrograph of a newt lung cell in early anaphase of mitosis. ... Cell migration is a central process in the development and maintenance of multicellular organisms. ...

The broad term 'VEGF' covers a number of proteins that result from alternate splicing of mRNA from a single, 8 exon, VEGF gene. The different VEGF splice variants are referred to by the number of amino acids they contain (in humans: VEGF₁₂₁, VEGF₁₄₅, VEGF₁₆₅, VEGF₁₈₉, VEGF₂₀₆; the rodent orthologs of these proteins contain one less amino acid). These proteins differ by the presence or absence of short C-terminal domains encoded by exons 6a, 6b and 7 of the VEGF gene. These domains have important functional consequences for the VEGF splice variants as they mediate interactions with heparan sulfate proteoglycans (HSPGs) and neuropilin co-receptors on the cell surface, enhancing their ability to bind and activate the VEGF signaling receptors (VEGFRs). In genetics, splicing is a modification of genetic information prior to translation. ... The interaction of mRNA in a eukaryote cell. ... Exons are the regions of DNA within a gene that are not spliced out from the transcribed RNA and are retained in the final messenger RNA (mRNA) molecule. ... Heparan Sulfate (HS) is a linear polysaccharide found in all animal tissues. ... Proteoglycans represent a special class of glycoprotein that are heavily glycosylated. ... Neuropilin is a protein receptor active in neurons. ...

The VEGF splice variants are released from cells as glycosylated disulfide-bonded homodimers. Structurally VEGF belongs to the PDGF family of cystine-knot growth factors. Subsequently, several closely-related proteins were discovered (Placenta growth factor (PlGF), VEGF-B, VEGF-C and VEGF-D) which together comprise the VEGF sub-family of growth factors. VEGF is sometimes referred to as VEGF-A to differentiate it from these related growth factors. A number of VEGF-related proteins have also been discovered encoded by viruses (VEGF-E) and in the venom of some snakes (VEGF-F). Platelet-derived growth factor (PDGF) is one of the numerous proteins that regulate cell growth and division. ...

All members of the VEGF family stimulate cellular responses by binding to tyrosine kinase receptors (the VEGFRs) on the cell surface, causing them to dimerize and become activated through transphosphorylation. The VEGF receptors have an extracellular portion consisting of 7 immunoglobulin-like domains, a single transmembrane spanning region and an intracellular portion containing a split tyrosine-kinase domain. VEGF-A binds to VEGFR-1 (Flt-1) and VEGFR-2 (KDR/Flk-1). VEGFR-2 appears to mediate almost all of the known cellular responses to VEGF. The function of VEGFR-1 is less well defined, although it is thought to modulate VEGFR-2 signaling. Another function of VEGFR-1 may be to act as a dummy/decoy receptor, sequestering VEGF from VEGFR-2 binding (this appears to be particularly important during vasculogenesis in the embryo). A third receptor has been discovered (VEGFR-3), however, VEGF-A is not a ligand for this receptor. VEGFR-3 mediates lymphangiogenesis in response to VEGF-C and VEGF-D. Tyrosine kinases are a subclass of protein kinase, see there for the principles of protein phosphorylation A tyrosine kinase (EC 2. ... Tyrosine kinases are a subclass of protein kinase, see there for the principles of protein phosphorylation A tyrosine kinase (EC 2. ... Lymphangiogesis is the formation of lymphatic vessels from a pre-existing lymphatic vessels, in a method believed to be similar to blood vessel development or angiogenesis. ...

VEGF production can be induced in cells that are not receiving enough oxygen. When a cell is deficient in oxygen, it produces HIF, Hypoxia Inducible Factor, a transcription factor. HIF stimulates the release of VEGF, among other functions (including modulation of erythropoeisis). Circulating VEGF then binds to VEGF Receptors on endothelial cells, triggering a Tyrosine Kinase Pathway leading to angiogenesis. General Name, Symbol, Number oxygen, O, 8 Chemical series Nonmetals, chalcogens Group, Period, Block 16, 2, p Appearance colorless (gas) very pale blue (liquid) Atomic mass 15. ... Hypoxia inducible factors (HIFs) are transcription factors that respond to changes in available oxygen in the cellular environment, specifically to decreases in oxygen, or hypoxia. ... Tyrosine kinases are a subclass of protein kinase, see there for the principles of protein phosphorylation A tyrosine kinase (EC 2. ...

VEGF has been implicated with poor prognosis in breast cancer. Numerous studies show a decreased OS and DFS in those tumors overexpressing VEGF. The overexpression of VEGF may be an early step in the process of metastasis, a step that is involved in the "angiogenic" switch. Although VEGF has been correlated with poor survival, its exact mechanism of action in the progression of tumors remains unclear. Metastasis (Greek: change of the state) is the spread of cancer from its primary site to other places in the body. ...

VEGF is also released in rheumatoid arthritis in response to TNF-α, increasing endothelial permeability and swelling and also stimulating angiogenesis (formation of capillaries).

VEGF is also important in diabetic retinopathy. The microcirculatory problems in the retina of people with diabetes can cause retinal ischaemia, which results in the release of VEGF. VEGF may then cause the creation of new blood vessels in the retina and elsewhere in the eye, heralding changes which may threaten the sight. Diabetic retinopathy is retinopathy (damage to the retina) caused by complications of diabetes mellitus, which could eventually lead to blindness. ... This article is about the disease that features high blood sugar. ...

Once released, VEGF may elicit several responses. It may cause a cell to survive, move, or further differentiate. Hence, VEGF is a potential target for the treatment of cancer. The first anti-VEGF drug, a monoclonal antibody named bevacizumab, was approved in 2004. Cells in culture, stained for keratin (red) and DNA (green). ... Cancer is a class of diseases or disorders characterized by uncontrolled division of cells and the ability of these cells to invade other tissues, either by direct growth into adjacent tissue through invasion or by implantation into distant sites by metastasis. ... Monoclonal antibodies (mAb) are antibodies that are identical because they were produced by one type of immune cell, all clones of a single parent cell. ... Bevacizumab (Avastin®) is an anti-angiogenesis drug used in treatment of cancer. ...

Current studies show that VEGFs are not the only promoters of angiogenesis. In particular FGF2 and HGF are potent angiogenic factors. Basic fibroblast growth factor, also known as bFGF or FGF2, is a member of the fibroblast growth factor family. ...

External links

• TherapeuticAngiogenesis.com
• ResearchVEGF.com