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Antiangiogenic effects of decorin restored by unfractionated, low molecular weight, and nonanticoagulant heparins

Amy K. L. Chui, Tilini N. Gunatillake, Vera Ignjatovic, Paul T. Monagle, Padma Murthi, Shaun P. Brennecke, John M. Whitelock and Joanne M. Said

Key Points

  • UFH, LMWH, and NAC restored angiogenesis in decorin-reduced endothelial cells.

  • NAC treatment was similar to, or better than, UFH or LMWH at improving endothelial angiogenesis without increasing anticoagulant activity.

Abstract

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.

  • Submitted January 3, 2017.
  • Accepted May 19, 2017.
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