Vascular endothelial growth factor
Vascular endothelial growth factor (VEGF,
It is part of the system that restores the oxygen supply to tissues when blood circulation is inadequate such as in hypoxic conditions.
History
In 1970, Judah Folkman et al. described a factor secreted by tumors causing angiogenesis and called it tumor angiogenesis factor.[4] In 1983 Senger et al. identified a vascular permeability factor secreted by tumors in guinea pigs and hamsters.[1] In 1989 Ferrara and Henzel described an identical factor in bovine pituitary follicular cells which they purified, cloned and named VEGF.[5] A similar VEGF alternative splicing was discovered by Tischer et al. in 1991.[6] Between 1996 and 1997, Christinger and De Vos obtained the crystal structure of VEGF, first at 2.5 Å resolution and later at 1.9 Å.[7][8][9]
Classification
In mammals, the VEGF family comprises five members:
Type | Function |
---|---|
VEGF-A
|
|
VEGF-B
|
Embryonic angiogenesis (myocardial tissue, to be specific)[16] |
VEGF-C
|
Lymphangiogenesis[17] |
VEGF-D
|
Needed for the development of lymphatic vasculature surrounding lung bronchioles [citation needed ]
|
PlGF
|
Important for Vasculogenesis, Also needed for angiogenesis during ischemia, inflammation, wound healing, and cancer. [citation needed] |
Activity of VEGF-A, as its name implies, has been studied mostly on cells of the vascular
Isoforms
There are multiple isoforms of VEGF-A that result from
Mechanism
All members of the VEGF family stimulate cellular responses by binding to
In addition to binding to
Expression
VEGF-A production can be induced in a cell that is not receiving enough
Clinical significance
In disease
VEGF-A and the corresponding receptors are rapidly up-regulated after traumatic injury of the central nervous system (CNS). VEGF-A is highly expressed in the acute and sub-acute stages of CNS injury, but the protein expression declines over time. This time-span of VEGF-A expression corresponds with the endogenous re-vascularization capacity after injury.[25] This would suggest that VEGF-A / VEGF165 could be used as target to promote angiogenesis after traumatic CNS injuries. However, there are contradicting scientific reports about the effects of VEGF-A treatments in CNS injury models.[25]
Although it has not been associated as a biomarker for the diagnosis of acute ischemic stroke,[29] if high levels of VEGF in serum in the first 48 hours have been associated with a poor prognosis in cerebral infarcts greater than 6 months[30] and 2 years.[31]
VEGF-A has been implicated with poor prognosis in breast cancer. Numerous studies show a decreased overall survival and disease-free survival in those tumors overexpressing VEGF. The overexpression of VEGF-A may be an early step in the process of metastasis, a step that is involved in the "angiogenic" switch. Although VEGF-A has been correlated with poor survival, its exact mechanism of action in the progression of tumors remains unclear.[32]
VEGF-A is also released in
VEGF-A is also important in diabetic retinopathy (DR). The microcirculatory problems in the retina of people with diabetes can cause retinal ischaemia, which results in the release of VEGF-A, and a switch in the balance of pro-angiogenic VEGFxxx isoforms over the normally expressed VEGFxxxb isoforms. VEGFxxx may then cause the creation of new blood vessels in the retina and elsewhere in the eye, heralding changes that may threaten the sight.
VEGF-A plays a role in the disease pathology of the wet form
VEGF-D serum levels are significantly elevated in patients with angiosarcoma.[34]
Once released, VEGF-A 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. Approximately 10–15% of patients benefit from bevacizumab therapy; however, biomarkers for bevacizumab efficacy are not yet known.
Current studies show that VEGFs are not the only promoters of angiogenesis. In particular,
Patients suffering from pulmonary emphysema have been found to have decreased levels of VEGF in the pulmonary arteries.
VEGF-D has also been shown to be over expressed in lymphangioleiomyomatosis and is currently used as a diagnostic biomarker in the treatment of this rare disease.[35]
In the kidney, increased expression of VEGF-A in glomeruli directly causes the glomerular hypertrophy that is associated with proteinuria.[36]
VEGF alterations can be predictive of early-onset pre-eclampsia.[37]
Gene therapies for refractory angina establish expression of VEGF in epicardial cells to promote angiogenesis.[38]
See also
- Proteases in angiogenesis
- Withaferin A, a potent inhibitor of angiogenesis
References
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Further reading
- Bengoetxea H, Argandoña EG, Lafuente JV (2008). "Effects of Visual Experience on Vascular Endothelial Growth Factor Expression during the Postnatal Development of the Rat Visual Cortex". Cerebral Cortex. 18 (7): 1630–39. PMID 17986606.
- Zan L, Wu H, Jiang J, Zhao S, Song Y, Teng G, Li H, Jia Y, Zhou M, Zhang X, Qi J, Wang J (2011). "Temporal profile of Src, SSeCKS, and angiogenic factors after focal cerebral ischemia: correlations with angiogenesis and cerebral edema". Neurochem. Int. 58 (8): 872–9. PMID 21334414.
- Zan L, Zhang X, Xi Y, Wu H, Song Y, Teng G, Li H, Qi J, Wang J (2014). "Src regulates angiogenic factors and vascular permeability after focal cerebral ischemia-reperfusion". Neuroscience. 262: 118–28. PMID 24412374.
- Wang J, Fu X, Jiang C, Yu L, Wang M, Han W, Liu L, Wang J (2014). "Bone marrow mononuclear cell transplantation promotes therapeutic angiogenesis via upregulation of the VEGF-VEGFR2 signaling pathway in a rat model of vascular dementia". Behav. Brain Res. 265: 171–80. PMID 24589546.
- Ferrara N, Gerber HP (2002). "The role of vascular endothelial growth factor in angiogenesis". Acta Haematol. 106 (4): 148–56. S2CID 46785882.
- Orpana A, Salven P (2003). "Angiogenic and lymphangiogenic molecules in hematological malignancies". Leuk. Lymphoma. 43 (2): 219–24. S2CID 21908151.
- Afuwape AO, Kiriakidis S, Paleolog EM (2003). "The role of the angiogenic molecule VEGF in the pathogenesis of rheumatoid arthritis". Histol. Histopathol. 17 (3): 961–72. PMID 12168808.
- de Bont ES, Neefjes VM, Rosati S, et al. (2003). "New vessel formation and aberrant VEGF/VEGFR signaling in acute leukemia: does it matter?". Leuk. Lymphoma. 43 (10): 1901–9. S2CID 45095413.
- Ria R, Roccaro AM, Merchionne F, et al. (2003). "Vascular endothelial growth factor and its receptors in multiple myeloma". Leukemia. 17 (10): 1961–6. S2CID 2335518.
- Caldwell RB, Bartoli M, Behzadian MA, et al. (2004). "Vascular endothelial growth factor and diabetic retinopathy: pathophysiological mechanisms and treatment perspectives". Diabetes Metab. Res. Rev. 19 (6): 442–55. S2CID 24931730.
- Patan, Sybill (2004). "Vasculogenesis and Angiogenesis". Angiogenesis in Brain Tumors. Cancer Treatment and Research. Vol. 117. pp. 3–32. PMID 15015550.
- Machein, Marcia Regina; Plate, Karl Heinz (2004). "Role of VEGF in Developmental Angiogenesis and in Tumor Angiogenesis in the Brain". Angiogenesis in Brain Tumors. Cancer Treatment and Research. Vol. 117. pp. 191–218. PMID 15015562.
- Eremina V, Quaggin SE (2004). "The role of VEGF-A in glomerular development and function". Curr. Opin. Nephrol. Hypertens. 13 (1): 9–15. S2CID 24212588.
- Storkebaum E, Lambrechts D, Carmeliet P (2004). "VEGF: once regarded as a specific angiogenic factor, now implicated in neuroprotection". BioEssays. 26 (9): 943–54. S2CID 871954.
- Ribatti D (2005). "The crucial role of vascular permeability factor/vascular endothelial growth factor in angiogenesis: a historical review". Br. J. Haematol. 128 (3): 303–9. S2CID 1906340.
- Loureiro RM, D'Amore PA (2005). "Transcriptional regulation of vascular endothelial growth factor in cancer". Cytokine Growth Factor Rev. 16 (1): 77–89. PMID 15733833.
- Herbst RS, Onn A, Sandler A (2005). "Angiogenesis and lung cancer: prognostic and therapeutic implications". J. Clin. Oncol. 23 (14): 3243–56. PMID 15886312.
- Pufe T, Kurz B, Petersen W, et al. (2006). "The influence of biomechanical parameters on the expression of VEGF and endostatin in the bone and joint system". Ann. Anat. 187 (5–6): 461–72. PMID 16320826.
- Tong JP, Yao YF (2006). "Contribution of VEGF and PEDF to choroidal angiogenesis: a need for balanced expressions". Clin. Biochem. 39 (3): 267–76. PMID 16409998.
- Lambrechts D, Carmeliet P (2007). "VEGF at the neurovascular interface: therapeutic implications for motor neuron disease". Biochim. Biophys. Acta. 1762 (11–12): 1109–21. PMID 16784838.
- Matsumoto T, Mugishima H (2006). "Signal transduction via vascular endothelial growth factor (VEGF) receptors and their roles in atherogenesis". J. Atheroscler. Thromb. 13 (3): 130–5. PMID 16835467.
- Bogaert E, Van Damme P, Van Den Bosch L, Robberecht W (2006). "Vascular endothelial growth factor in amyotrophic lateral sclerosis and other neurodegenerative diseases". Muscle Nerve. 34 (4): 391–405. S2CID 22086357.
- Mercurio AM, Lipscomb EA, Bachelder RE (2006). "Non-angiogenic functions of VEGF in breast cancer". Journal of Mammary Gland Biology and Neoplasia. 10 (4): 283–90. S2CID 16565983.
- Makinde T, Murphy RF, Agrawal DK (2007). "Immunomodulatory role of vascular endothelial growth factor and angiopoietin-1 in airway remodeling". Curr. Mol. Med. 6 (8): 831–41. PMID 17168735.
- Rini BI, Rathmell WK (2007). "Biological aspects and binding strategies of vascular endothelial growth factor in renal cell carcinoma". Clin. Cancer Res. 13 (2 Pt 2): 741s–746s. PMID 17255303.
- Jiang, Chao; Zuo, Fangfang; Wang, Yuejuan; Lu, Hong; Yang, Qingwu; Wang, Jian (1 January 2017). "Progesterone Changes VEGF and BDNF Expression and Promotes Neurogenesis After Ischemic Stroke". Molecular Neurobiology. 54 (1): 571–581. PMID 26746666.
- Rodgers LS, Lalani S, Hardy KM, Xiang X, Broka D, Antin PB, Camenisch TD (2006). "Depolymerized hyaluronan induces vascular endothelial growth factor, a negative regulator of developmental epithelial-to-mesenchymal transformation". Circ. Res. 99 (6): 583–9. PMID 16931798.
- Qaum, T; Xu, Q; Joussen, AM; et al. (2001). "VEGF-initiated blood-retinal barrier breakdown in early diabetes". Invest Ophthalmol Vis Sci. 42 (10): 2408–2413. PMID 11527957.
External links
- Vascular+Endothelial+Growth+Factors at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Proteopedia Vascular_Endothelial_Growth_Factor – the Vascular Endothelial Growth Factor Structure in Interactive 3D