期刊
CLINICAL SCIENCE
卷 110, 期 5, 页码 575-585出版社
PORTLAND PRESS LTD
DOI: 10.1042/CS20050292
关键词
pre-eclampsia; splice variant; vascular endothelial growth factor (VEGF); vascular permeability
资金
- Wellcome Trust [69029] Funding Source: Medline
PET (pre-eclamptic toxaemia) has recently been linked with alterations in production of a VEGFRI [VEGF (vascular endothelial growth factor) receptor I] splice variant that acts as a circulating inhibitor. We have recently described a family of naturally occurring splice variants of VEGR termed VEGF(xxx)b, that also appear to act as inhibitors of conventional VEGF(xxx)-mediated angiogenesis. To determine whether alteration in splicing of VEGF-VEGFR family members extended beyond VEGFRI, we investigated the effect of pre-eclampsia on placental VEGF(xxx)b mRNA and protein expression. VEGF(xxx) and VEGF(xxx)b mRNA and protein were both found in normal human term placentae. VEGF(xxx) protein formed the majority of the total VEGF protein (980 +/- 195 pg/mg), whereas VEGF(xxx)b (11.5 pg/mg) was found to form a small part of the total VEGF protein expression (1.5 +/- 0.24%). Evidence for VEGF(165)b, VEGF(121)b and VEGF(145)b expression was found. In pre-eclamptic placentae, there was a significant down-regulation of VEGF(xxx)b isoforms, but a small up-regulation of VEGF(xxx) isoforms. In normal placenta VEGF(xxx)b and VEGF(xxx) concentrations were positively correlated (r = 0.69, P < 0.02), whereas in pre-eclamptic placentae, there was a significant negative correlation between VEGF(xxx)b and VEGF(xxx). protein expression (r = -0.8, P < 0.02), indicating that there was a significant uncoupling of the splicing regulation of the VEGF isoforms. Combined with previous studies showing increased soluble VEGFRI isoforms in human pre-eclampsia, these data suggest that there may be a common mechanism in pre-eclampsia that involves dysregulation of mRNA splicing of members of the VEGF-VEGFR axis.
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