Abstract 12903: Low-molecular Weight Heparin Improves Endothelial Function in Pregnant Women at High-risk of Preeclampsia

Abstract

Introduction: Women who develop preeclampsia (PE) demonstrate cardiovascular abnormalities during pregnancy and postpartum. Low-molecular weight heparin (LMWH) significantly reduces the incidence of PE, although the mechanisms of action are unknown. Hypothesis: LMWH improves cardiovascular function in pregnant women at high-risk of PE. Methods: Pregnant women at high-risk of PE (n=25) and low-risk pregnant controls (n=20) at 22-26 weeks’ gestation underwent cardiovascular assessments. High-risk women were then randomized to LMWH or saline placebo (30mg IV bolus and 1mg/kg subcutaneous dose). Cardiovascular function was assessed 1 and 3 hours post-randomization. The in vitro endothelial effects of patient serum and LMWH on human umbilical venous endothelial cells (HUVEC) were determined through angiogenesis assays, gene expression and protein secretion. Results: High-risk women demonstrated a low-volume, high resistance hemodynamic profile with significantly impaired radial artery flow-mediated dilation (FMD) when compared to low-risk controls (6.5±0.9% vs 9.7±1.0%, P=0.03). Baseline plasma and urine levels of placental growth factor (PlGF) were significantly lower in high-risk women compared with controls (P=0.003 and P=0.01, respectively). LMWH significantly increased FMD in high-risk women following randomization compared to baseline (10.8±1.0% vs 7.6±1.0%, P=0.008). LMWH also significantly increased plasma levels of PlGF, soluble fms-like tyrosine kinase-1 and myeloperoxidase (P=0.006, P=0.03 and P=0.03, respectively). Serum from high-risk women significantly impaired HUVEC angiogenesis and significantly increased PlGF-1 and PlGF-2 transcription compared to serum from controls (0.79±0.05 vs 0.99±0.05, P=0.03; P=0.03 and P=0.01, respectively). Co-exposure of high-risk serum with LMWH improved the in vitro angiogenic response such that it was equivalent to that of control serum and promoted PlGF secretion. Conclusions: Our data indicate that LMWH improves maternal endothelial function in pregnant women at high-risk of developing PE, possibly mediated through increased PlGF bioavailability. Future trials are needed to assess the effectiveness of LMWH for the prevention of severe PE in screen-positive women.