PMID- 29296764 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20191120 IS - 2473-9529 (Print) IS - 2473-9537 (Electronic) IS - 2473-9529 (Linking) VI - 1 IP - 16 DP - 2017 Jul 11 TI - Antiangiogenic effects of decorin restored by unfractionated, low molecular weight, and nonanticoagulant heparins. PG - 1243-1253 LID - 10.1182/bloodadvances.2017004333 [doi] AB - Pregnancies affected by preeclampsia (PE) or fetal growth restriction (FGR) display increases in thrombin generation and reductions in angiogenesis and cell growth. There is significant interest in the potential for low molecular weight heparins (LMWHs) to reduce the recurrence of PE and FGR. However, LMWH is associated with an increased risk of bleeding. Therefore, it is of vital importance to determine the exact molecular function of heparins in pregnancy if they are used as therapy for pregnant women. We aimed to determine this using our model for PE/FGR in microvascular endothelial cells. The expression of decorin, a proteoglycan, was reduced to mimic PE/FGR in these cells compared with controls. Four concentrations of unfractionated heparin (UFH), LMWH, and nonanticoagulant heparin (NAC) were added to determine the effect on thrombin generation, angiogenesis, and cell growth. Treatment with UFH and LMWH reduced thrombin generation and restored angiogenesis but decreased cell growth. Treatment with NAC did not affect thrombin generation, restored angiogenesis, and showed a trend toward cell growth. In conclusion, treatment with NAC produced the same, if not better, results as treatment with UFH or LMWH, without the same impact on coagulation. Therefore, NAC could potentially be a better therapeutic option for prevention of PE/FGR in high-risk women, without the risk of the adverse effects of traditional anticoagulants. FAU - Chui, Amy K L AU - Chui AKL AD - Department of Obstetrics and Gynaecology, Sunshine Hospital, The University of Melbourne, St Albans, VIC, Australia. FAU - Gunatillake, Tilini N AU - Gunatillake TN AD - Department of Obstetrics and Gynaecology, Sunshine Hospital, The University of Melbourne, St Albans, VIC, Australia. FAU - Ignjatovic, Vera AU - Ignjatovic V AD - Department of Clinical Haematology and. AD - Department of Paediatrics, Murdoch Childrens Research Institute, The Royal Children's Hospital, The University of Melbourne, Parkville, VIC, Australia. FAU - Monagle, Paul T AU - Monagle PT AD - Department of Clinical Haematology and. AD - Department of Paediatrics, Murdoch Childrens Research Institute, The Royal Children's Hospital, The University of Melbourne, Parkville, VIC, Australia. FAU - Murthi, Padma AU - Murthi P AD - Department of Medicine, School of Clinical Sciences, Monash University, Clayton, VIC, Australia. AD - The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, Australia. AD - Department of Maternal-Fetal Medicine Pregnancy Research Centre, The Royal Women's Hospital, Parkville, VIC, Australia. FAU - Brennecke, Shaun P AU - Brennecke SP AD - Department of Maternal-Fetal Medicine Pregnancy Research Centre, The Royal Women's Hospital, Parkville, VIC, Australia. AD - Department of Obstetrics and Gynaecology, The Royal Women's Hospital, The University of Melbourne, Parkville, VIC, Australia. FAU - Whitelock, John M AU - Whitelock JM AD - Graduate School of Biomedical Engineering, University of New South Wales, Kensington, NSW, Australia; and. FAU - Said, Joanne M AU - Said JM AD - Department of Obstetrics and Gynaecology, Sunshine Hospital, The University of Melbourne, St Albans, VIC, Australia. AD - Maternal Fetal Medicine, Sunshine Hospital, St Albans, VIC, Australia. LA - eng PT - Journal Article DEP - 20170703 PL - United States TA - Blood Adv JT - Blood advances JID - 101698425 PMC - PMC5728543 COIS- Conflict-of-interest disclosure: The authors declare no competing financial interests. EDAT- 2018/01/04 06:00 MHDA- 2018/01/04 06:01 PMCR- 2017/07/03 CRDT- 2018/01/04 06:00 PHST- 2017/01/03 00:00 [received] PHST- 2017/05/19 00:00 [accepted] PHST- 2018/01/04 06:00 [entrez] PHST- 2018/01/04 06:00 [pubmed] PHST- 2018/01/04 06:01 [medline] PHST- 2017/07/03 00:00 [pmc-release] AID - 2017/004333 [pii] AID - 10.1182/bloodadvances.2017004333 [doi] PST - epublish SO - Blood Adv. 2017 Jul 3;1(16):1243-1253. doi: 10.1182/bloodadvances.2017004333. eCollection 2017 Jul 11.