Platelet-activating factor enhances the expression of vascular endothelial growth factor in normal human astrocytes under hypoxia

Platelet-activating factor (PAF) has neuroregulatory activities and is implicated in ischemic injury of the brain. We found that PAF stimulates the expression of vascular endothelial growth factor (VEGF), a potent and specific mitogen for vascular endothelial cells, in normal human astrocytes. Reverse transcription-PCR (RT-PCR) demonstrated the enhancement, by PAF, of the VEGF mRNA expression in time- and concentration-dependent manners. The levels of VEGF protein in astrocyte-conditioned medium were determined by enzyme-linked immunosorbent assay, and 24-h stimulation with 10 nM PAF resulted in 1.3-fold increase in VEGF protein production. When the cells were subjected to hypoxia, the PAF-induced production of VEGF was enhanced by 6.7-fold as compared to the cells stimulated in a similar manner under normoxia. PAF stimulates VEGF expression in human astrocytes, and hypoxia exerts a synergistic effect on the PAF-induced VEGF expression. PAF is known as a mediator of ischemic injury of the nervous tissues, and VEGF may be involved in part of the effect of PAF in brain hypoxia. (C) 2003 Elsevier Science B.V. All rights reserved.