The role of vascular endothelial growth factor in cerebral oedema formation.
Cerebral oedema induced by hypoxia is connected with activity of vascular endothelial growth factor (VEGF). Hypoxia activates VEGF expression, which leads to the increase of endothelial permeability. Hypoxia-induced VEGF overexpression is connected with transcriptional activation by hypoxia-inducible factor 1 (HIF-1) and posttranscriptional stabilisation of mRNA by proteins such as HuR. Also a number of VEGF receptors increases in response to hypoxia. Transcriptional activation by HIF-1 (receptor flt-1) and posttranscriptional mechanism (receptor KDR) play a key role in this process. Vascular endothelial growth factor increases the permeability and this process is very effective in hypoxia, which prevents the rapid autooxidation of the second messenger NO. Many VEGF inhibitors can be used in future for prevention or treatment of hypoxia-induced cerebral oedema. They can inhibit VEGF formation (as used in cerebral oedema dexamethason, or barbiturates, trichstatin A, candesartan, small molecule inhibitors of hypoxia-inducible factor 1, gelandamycin, antysenses, rybosymes and catechins) or VEGF activity (soluble receptors, monoclonal antibodies, heterodimeric antagonistic VEGF variant, RTK inhibitors and catechins).
Jośko
Jadwiga
J
Department of Environmental Medicine and Epidemiology, Medical University of Silesia, Zabrze, Poland. medsrod@infomed.slam.katowice.pl
Knefel
Krzysztof
K
D000818:Animals; D001929:Brain Edema / Q000378:metabolism* / Q000628:therapy; D006801:Humans; D002534:Hypoxia, Brain / Q000378:metabolism / Q000628:therapy; D040262:Receptors, Vascular Endothelial Growth Factor / Q000096:biosynthesis; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000502:physiology*
D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor