Abstract
Low molecular weight heparin (LMWH) is being investigated as a potential preventative therapy against preeclampsia. There is evidence suggesting that LMWH may prevent preeclampsia through anticoagulation-independent mechanisms. In this study, we compared the in vitro placental, endothelial, and anti-inflammatory effects of a LMWH (dalteparin) with a non-anticoagulant, glycol-split heparin derivative (gsHep). In contrast with dalteparin, gsHep did not interact with antithrombin III, possess significant anti-Factor Xa activity, or significantly prolong in vitro plasma clotting time. However, dalteparin and gsHep were otherwise mechanistically similar, both interacting with soluble fms-like tyrosine kinase-1 (sFlt1) and promoting release of the pro-angiogenic protein placental growth factor, but not the anti-angiogenic sFlt1, from healthy placental villous explants. Placental explant media pre-treated with dalteparin or gsHep significantly stimulated endothelial cell tube formation compared to untreated explants. Lastly, dalteparin and gsHep both significantly suppressed inflammation by inhibiting complement activation and leukocyte adhesion to endothelial cells that were activated using serum from preeclamptic women. Our data suggest that non-anticoagulant heparin derivatives may be utilized as a tool to distinguish the anticoagulation-independent mechanisms of LMWH, and provide insight into the role of anticoagulation in the prevention of preeclampsia.
Original language | English |
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Pages (from-to) | 1082-1090 |
Number of pages | 9 |
Journal | Biology of Reproduction |
Volume | 99 |
Issue number | 5 |
Early online date | 30 May 2018 |
DOIs | |
Publication status | Published - 1 Nov 2018 |
Bibliographical note
The authors thank the donors, the Research Centre for Women’s and Infants’ Health BioBank program, the Lunenfeld-Tanenbaum Research Institute and the MSH/University Health Network Department of Obstetrics & Gynaecology for the human specimens used in this study.Keywords
- preeclampsia
- placenta
- angiogenesis
- immunology
- molecular biology
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Iain Greig
- School of Medicine, Medical Sciences & Nutrition, Microbiology and Immunity
- School of Medicine, Medical Sciences & Nutrition, Medical Sciences - Reader
- School of Medicine, Medical Sciences & Nutrition, Institute of Medical Sciences
Person: Academic, Academic Related - Research