The role of heparin and heparin-binding growth factors in pre-eclampsia

The aims of this study tested the hypothesis that expression of heparin-binding growth factors (HBGFs) in normal placental development was altered in a specific pregnancy disorder preeclampsia. HBGFs bind to heparin, a glycosaminoglycan (GAG) affecting activity. I investigated the role of heparin and HBGFs in pathophysiology of pre-eclampsia. Placental tissue from a cohort study of 87 women was performed following uncomplicated pregnancy at term, but not in labour (TNL, n=26), preterm labour (PTL, n=17), following labour onset (TL, n=21), first trimester (FNL, n=4) and pre-eclampsia (PE, n=19). The HBGFs studied were vascular endothelial growth factor (VEGF), placental growth factor (PLGF), fibroblast growth factor 2 (FGF2), hepatocyte growth factor (HGF), platelet-derived growth factor (PDGF), heparin-binding epidermal growth factor (HB-EGF), midkine (MK), pleiotrophin (PTN), and cluster differentiation (CD105). The localisation of HBGFs and receptors VEGFR-1, /(sflt-1), PLGFR-1, VEGFR-2 and FGF2R-1 in placenta were detected. The expression of VEGF, PLGF, FGF2, HGF, PDGF, CD105 was confined to villous trophoblast, endothelial cells except for MK, HB-EGF and PTN was specifically to villous trophoblast. The total RNA production in human placentae samples (n=7) from PE and controls were analysed using qRTPCR. Placental expression of mRNA was extracted for primer assays of PLGF, FGF2, MK, PTN, and endogenous housekeeping gene as Succinate dehydrogenase complex subunit A (SDHA). FGF2 and SDHA mRNA expression was significantly different using Mann-Whitney U test. An in vitro villous trophoblast invasion model was performed with human fibrosarcoma HT1080 invasive cells (positive control), mouse embryonic fibroblast NIH/3T3 non-invasive cells (negative control) and immortalised human primary villous trophoblastic cell lines TCL-1.The greatest stimulation was by FGF2, PDGF-BB, HGF, MK and co-incubation with heparin enhanced these responses, except for PTN using the Mann-Whitney U test. Heparin’s role is indicated in mediating the effects of HBGFs. It’s suggests heparin therapeutic use in the treatment of pre-eclampsia.