Vascular endothelial growth factor B explained

Vascular endothelial growth factor B also known as VEGF-B is a protein that, in humans, is encoded by the VEGF-B gene.^[1] VEGF-B is a growth factor that belongs to the vascular endothelial growth factor family, of which VEGF-A is the best-known member.

Function

In contrast to VEGF-A, VEGF-B plays a less pronounced role in the vascular system: Whereas VEGF-A is important for the formation of blood vessels, such as during development or in pathological conditions, VEGF-B seems to play a role only in the maintenance of newly formed blood vessels during pathological conditions.^[2] VEGF-B plays also an important role on several types of neurons. It is important for the protection of neurons in the retina^[3] and the cerebral cortex during stroke,^[4] and of motor neurons during motor neuron diseases such as amyotrophic lateral sclerosis.^[5]

VEGF-B exerts its effects via the FLT1 receptor.^[6] But the role of co-receptor NRP in VEGF-B-mediated effects is still unclear.^[7]

VEGF-B has also been found to control endothelial uptake and transport of fatty acids in heart and skeletal muscle.^{[8] [9]}

Interactions

Vascular endothelial growth factor B has been shown to interact with FLT1, NRP1 and NRP2.^{[10] [11] [12] [13]}

Further reading

• Poesen K, Lambrechts D, Van Damme P, Dhondt J, Bender F, Frank N, Bogaert E, Claes B, Heylen L, Verheyen A, Raes K, Tjwa M, Eriksson U, Shibuya M, Nuydens R, Van Den Bosch L, Meert T, D'Hooge R, Sendtner M, Robberecht W, Carmeliet P . 6 . Novel role for vascular endothelial growth factor (VEGF) receptor-1 and its ligand VEGF-B in motor neuron degeneration . The Journal of Neuroscience . 28 . 42 . 10451–10459 . October 2008 . 18923022 . 6671326 . 10.1523/JNEUROSCI.1092-08.2008 . free .
• Joukov V, Kaipainen A, Jeltsch M, Pajusola K, Olofsson B, Kumar V, Eriksson U, Alitalo K . 6 . Vascular endothelial growth factors VEGF-B and VEGF-C . Journal of Cellular Physiology . 173 . 2 . 211–215 . November 1997 . 9365524 . 10.1002/(SICI)1097-4652(199711)173:2<211::AID-JCP23>3.0.CO;2-H . 2930599 .
• Olofsson B, Pajusola K, Kaipainen A, von Euler G, Joukov V, Saksela O, Orpana A, Pettersson RF, Alitalo K, Eriksson U . 6 . Vascular endothelial growth factor B, a novel growth factor for endothelial cells . Proceedings of the National Academy of Sciences of the United States of America . 93 . 6 . 2576–2581 . March 1996 . 8637916 . 39839 . 10.1073/pnas.93.6.2576 . 1996PNAS...93.2576O . free .
• Olofsson B, Pajusola K, von Euler G, Chilov D, Alitalo K, Eriksson U . Genomic organization of the mouse and human genes for vascular endothelial growth factor B (VEGF-B) and characterization of a second splice isoform . The Journal of Biological Chemistry . 271 . 32 . 19310–19317 . August 1996 . 8702615 . 10.1074/jbc.271.32.19310 . free .
• Grimmond S, Lagercrantz J, Drinkwater C, Silins G, Townson S, Pollock P, Gotley D, Carson E, Rakar S, Nordenskjöld M, Ward L, Hayward N, Weber G . 6 . Cloning and characterization of a novel human gene related to vascular endothelial growth factor . Genome Research . 6 . 2 . 124–131 . February 1996 . 8919691 . 10.1101/gr.6.2.124 . free .
• Olofsson B, Korpelainen E, Pepper MS, Mandriota SJ, Aase K, Kumar V, Gunji Y, Jeltsch MM, Shibuya M, Alitalo K, Eriksson U . 6 . Vascular endothelial growth factor B (VEGF-B) binds to VEGF receptor-1 and regulates plasminogen activator activity in endothelial cells . Proceedings of the National Academy of Sciences of the United States of America . 95 . 20 . 11709–11714 . September 1998 . 9751730 . 21705 . 10.1073/pnas.95.20.11709 . 1998PNAS...9511709O . free .
• Makinen T, Olofsson B, Karpanen T, Hellman U, Soker S, Klagsbrun M, Eriksson U, Alitalo K . 6 . Differential binding of vascular endothelial growth factor B splice and proteolytic isoforms to neuropilin-1 . The Journal of Biological Chemistry . 274 . 30 . 21217–21222 . July 1999 . 10409677 . 10.1074/jbc.274.30.21217 . free .
• Ikuta T, Ariga H, Matsumoto K . Extracellular matrix tenascin-X in combination with vascular endothelial growth factor B enhances endothelial cell proliferation . Genes to Cells . 5 . 11 . 913–927 . November 2000 . 11122379 . 10.1046/j.1365-2443.2000.00376.x . 41366972 . free .
• Qi JH, Ebrahem Q, Moore N, Murphy G, Claesson-Welsh L, Bond M, Baker A, Anand-Apte B . 6 . A novel function for tissue inhibitor of metalloproteinases-3 (TIMP3): inhibition of angiogenesis by blockage of VEGF binding to VEGF receptor-2 . Nature Medicine . 9 . 4 . 407–415 . April 2003 . 12652295 . 10.1038/nm846 . 12563403 .
• Trompezinski S, Berthier-Vergnes O, Denis A, Schmitt D, Viac J . Comparative expression of vascular endothelial growth factor family members, VEGF-B, -C and -D, by normal human keratinocytes and fibroblasts . Experimental Dermatology . 13 . 2 . 98–105 . February 2004 . 15009103 . 10.1111/j.0906-6705.2004.00137.x . 13040175 .
• Timoshenko AV, Chakraborty C, Wagner GF, Lala PK . COX-2-mediated stimulation of the lymphangiogenic factor VEGF-C in human breast cancer . British Journal of Cancer . 94 . 8 . 1154–1163 . April 2006 . 16570043 . 2361247 . 10.1038/sj.bjc.6603067 .
• Iyer S, Scotney PD, Nash AD, Ravi Acharya K . Crystal structure of human vascular endothelial growth factor-B: identification of amino acids important for receptor binding . Journal of Molecular Biology . 359 . 1 . 76–85 . May 2006 . 16616187 . 10.1016/j.jmb.2006.03.002 .
• Yamada E, Yamazaki K, Takano K, Obara T, Sato K . Iodide inhibits vascular endothelial growth factor-A expression in cultured human thyroid follicles: a microarray search for effects of thyrotropin and iodide on angiogenesis factors . Thyroid . 16 . 6 . 545–554 . June 2006 . 16839256 . 10.1089/thy.2006.16.545 .
• de Paulis A, Prevete N, Fiorentino I, Rossi FW, Staibano S, Montuori N, Ragno P, Longobardi A, Liccardo B, Genovese A, Ribatti D, Walls AF, Marone G . 6 . Expression and functions of the vascular endothelial growth factors and their receptors in human basophils . Journal of Immunology . 177 . 10 . 7322–7331 . November 2006 . 17082651 . 10.4049/jimmunol.177.10.7322 . free .

External links

• PDBe-KB provides an overview of all the structure information available in the PDB for Human Vascular endothelial growth factor B

Notes and References

1. Web site: Entrez Gene: VEGFB vascular endothelial growth factor B.
2. Zhang F, Tang Z, Hou X, Lennartsson J, Li Y, Koch AW, Scotney P, Lee C, Arjunan P, Dong L, Kumar A, Rissanen TT, Wang B, Nagai N, Fons P, Fariss R, Zhang Y, Wawrousek E, Tansey G, Raber J, Fong GH, Ding H, Greenberg DA, Becker KG, Herbert JM, Nash A, Yla-Herttuala S, Cao Y, Watts RJ, Li X . 6 . VEGF-B is dispensable for blood vessel growth but critical for their survival, and VEGF-B targeting inhibits pathological angiogenesis . Proceedings of the National Academy of Sciences of the United States of America . 106 . 15 . 6152–6157 . April 2009 . 19369214 . 2669337 . 10.1073/pnas.0813061106 . 2009PNAS..106.6152Z . free .
3. Li Y, Zhang F, Nagai N, Tang Z, Zhang S, Scotney P, Lennartsson J, Zhu C, Qu Y, Fang C, Hua J, Matsuo O, Fong GH, Ding H, Cao Y, Becker KG, Nash A, Heldin CH, Li X . 6 . VEGF-B inhibits apoptosis via VEGFR-1-mediated suppression of the expression of BH3-only protein genes in mice and rats . The Journal of Clinical Investigation . 118 . 3 . 913–923 . March 2008 . 18259607 . 2230661 . 10.1172/JCI33673 .
4. Sun Y, Jin K, Childs JT, Xie L, Mao XO, Greenberg DA . Increased severity of cerebral ischemic injury in vascular endothelial growth factor-B-deficient mice . Journal of Cerebral Blood Flow and Metabolism . 24 . 10 . 1146–1152 . October 2004 . 15529014 . 10.1097/01.wcb.0000134477.38980.38 . free .
5. Poesen K, Lambrechts D, Van Damme P, Dhondt J, Bender F, Frank N, Bogaert E, Claes B, Heylen L, Verheyen A, Raes K, Tjwa M, Eriksson U, Shibuya M, Nuydens R, Van Den Bosch L, Meert T, D'Hooge R, Sendtner M, Robberecht W, Carmeliet P . 6 . Novel role for vascular endothelial growth factor (VEGF) receptor-1 and its ligand VEGF-B in motor neuron degeneration . The Journal of Neuroscience . 28 . 42 . 10451–10459 . October 2008 . 18923022 . 6671326 . 10.1523/JNEUROSCI.1092-08.2008 . free .
6. Yamazaki Y, Morita T . Molecular and functional diversity of vascular endothelial growth factors . Molecular Diversity . 10 . 4 . 515–527 . November 2006 . 16972015 . 10.1007/s11030-006-9027-3 . 28692204 .
7. Mallick R, Ylä-Herttuala S . Therapeutic Potential of VEGF-B in Coronary Heart Disease and Heart Failure: Dream or Vision? . Cells . 11 . 24 . 4134 . December 2022 . 36552897 . 10.3390/cells11244134 . 9776740 . free .
8. Muoio DM . Deborah Muoio. Metabolism and vascular fatty acid transport . The New England Journal of Medicine . 363 . 3 . 291–293 . July 2010 . 20647206 . 10.1056/NEJMcibr1005397 .
9. Hagberg CE, Mehlem A, Falkevall A, Muhl L, Fam BC, Ortsäter H, Scotney P, Nyqvist D, Samén E, Lu L, Stone-Elander S, Proietto J, Andrikopoulos S, Sjöholm A, Nash A, Eriksson U . 6 . Targeting VEGF-B as a novel treatment for insulin resistance and type 2 diabetes . Nature . 490 . 7420 . 426–430 . October 2012 . 23023133 . 10.1038/nature11464 . 2012Natur.490..426H . 4315297 .
10. Olofsson B, Korpelainen E, Pepper MS, Mandriota SJ, Aase K, Kumar V, Gunji Y, Jeltsch MM, Shibuya M, Alitalo K, Eriksson U . 6 . Vascular endothelial growth factor B (VEGF-B) binds to VEGF receptor-1 and regulates plasminogen activator activity in endothelial cells . Proceedings of the National Academy of Sciences of the United States of America . 95 . 20 . 11709–11714 . September 1998 . 9751730 . 21705 . 10.1073/pnas.95.20.11709 . 1998PNAS...9511709O . free .
11. Makinen T, Olofsson B, Karpanen T, Hellman U, Soker S, Klagsbrun M, Eriksson U, Alitalo K . 6 . Differential binding of vascular endothelial growth factor B splice and proteolytic isoforms to neuropilin-1 . The Journal of Biological Chemistry . 274 . 30 . 21217–21222 . July 1999 . 10409677 . 10.1074/jbc.274.30.21217 . free .
12. Mallick R, Ylä-Herttuala S . Therapeutic Potential of VEGF-B in Coronary Heart Disease and Heart Failure: Dream or Vision? . Cells . 11 . 24 . 4134 . December 2022 . 36552897 . 9776740 . 10.3390/cells11244134 . free .
13. Mallick R, Gurzeler E, Toivanen PI, Nieminen T, Ylä-Herttuala S . Novel Designed Proteolytically Resistant VEGF-B186R127S Promotes Angiogenesis in Mouse Heart by Recruiting Endothelial Progenitor Cells . Frontiers in Bioengineering and Biotechnology . 10 . 907538 . 2022-08-04 . 35992336 . 9385986 . 10.3389/fbioe.2022.907538 . free .