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

Abstract

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.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 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.

Molecular actions of heparin and their implications in preventing pre‐eclampsia

“…Conditioned medium from first‐trimester placental villous explants treated with dalteparin also stimulated endothelial tube formation as compared to medium that was untreated . In direct support of the notion that LMWH may protect against pre‐eclampsia through non‐anticoagulant mechanisms, a recent study showed that a chemically modified, non‐anticoagulant derivative of heparin can reverse the antiangiogenic properties of decorin‐reduced endothelial cells similarly to dalteparin . Interestingly, in a rat mesentery angiogenesis assay, dalteparin significantly stimulated angiogenesis in an inversely dose‐dependent manner at therapeutically relevant levels, ranging from prophylactic to maximum clinically acceptable doses .…”

Effects of Low-Molecular Heparin on Pregnant Women with Factor V Mutation (GA Genotype)

“…One can also draw attention to the fact that the increase in thrombin potential is characteristic for the development of preeclampsia [49,50], and LMWH improves angiogenesis by lowering thrombin generation [51].…”