Effects of glycol-split low molecular weight heparin on placental, endothelial, and anti-inflammatory pathways relevant to preeclampsia

Jovian M. Wat, Krista Hawrylyshyn, Dora Baczyk, Iain R. Greig, John C. Kingdom (Corresponding Author)

Research output: Contribution to journalArticle

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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 languageEnglish
Pages (from-to)1082-1090
Number of pages9
JournalBiology of Reproduction
Volume99
Issue number5
Early online date30 May 2018
DOIs
Publication statusPublished - 1 Nov 2018

Fingerprint

Dalteparin
Glycols
Low Molecular Weight Heparin
Pre-Eclampsia
Heparin
Anti-Inflammatory Agents
Vascular Endothelial Growth Factor Receptor-1
Endothelial Cells
Angiogenic Proteins
Factor Xa
Antithrombin III
Complement Activation
Intercellular Signaling Peptides and Proteins
Leukocytes
Inflammation
Serum

Keywords

  • preeclampsia
  • placenta
  • angiogenesis
  • immunology
  • molecular biology

Cite this

Effects of glycol-split low molecular weight heparin on placental, endothelial, and anti-inflammatory pathways relevant to preeclampsia. / Wat, Jovian M.; Hawrylyshyn, Krista; Baczyk, Dora; Greig, Iain R.; Kingdom, John C. (Corresponding Author).

In: Biology of Reproduction, Vol. 99, No. 5, 01.11.2018, p. 1082-1090.

Research output: Contribution to journalArticle

Wat, Jovian M. ; Hawrylyshyn, Krista ; Baczyk, Dora ; Greig, Iain R. ; Kingdom, John C. / Effects of glycol-split low molecular weight heparin on placental, endothelial, and anti-inflammatory pathways relevant to preeclampsia. In: Biology of Reproduction. 2018 ; Vol. 99, No. 5. pp. 1082-1090.
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