title: Low Molecular Weight Heparin Improves Endothelial Function in Pregnant Women at High Risk of Preeclampsia.
abstract: Low molecular weight heparin (LMWH) has been investigated for the prevention of severe preeclampsia, although the mechanisms of action are unknown. The objective of this study was to investigate the cardiovascular effects of LMWH in pregnant women at high risk of preeclampsia. Pregnant women at high risk of preeclampsia (n=25) and low-risk pregnant controls (n=20) at 22 to 26 weeks' gestation underwent baseline cardiovascular assessments. High-risk women were then randomized to LMWH or saline placebo (30 mg IV bolus and 1 mg/kg subcutaneous dose). Cardiovascular function was assessed 1 and 3 hours post randomization. The in vitro endothelial effects of patient serum and exogenous LMWH on human umbilical venous endothelial cells were determined. High-risk women demonstrated a reduced cardiac output, high resistance hemodynamic profile with impaired radial artery flow-mediated dilation compared with controls. LMWH increased flow-mediated dilation in high-risk women 3 hours after randomization compared with baseline and increased plasma levels of placental growth factor, soluble fms-like tyrosine kinase-1, and myeloperoxidase. Serum from high-risk women impaired endothelial cell angiogenesis and increased PlGF-1 and PlGF-2 transcription compared with serum from low-risk controls. Coexposure of high-risk serum with LMWH improved the in vitro angiogenic response such that it was equivalent to that of low-risk serum and promoted placental growth factor secretion. LMWH improves maternal endothelial function in pregnant women at high risk of developing preeclampsia, possibly mediated through increased placental growth factor bioavailability.
authors.affiliation: From the Division of Cardiology, Department of Medicine, Mount Sinai Hospital (K.M., J.D.P.), The Centre for Women's and Infant's Health at the Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital (K.M., D.B., A.P., J.C.P.K.), Department of Pharmacology and Toxicology (K.M., J.D.P.), Division of Nephrology and Obstetrical Medicine, Sunnybrook Health Sciences Centre (M.H.), and Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynaecology, Mount Sinai Hospital (J.C.P.K.), University of Toronto, Ontario, Canada.
authors.forename: Kelsey
authors.initials: K
authors.lastname: McLaughlin
authors.affiliation: From the Division of Cardiology, Department of Medicine, Mount Sinai Hospital (K.M., J.D.P.), The Centre for Women's and Infant's Health at the Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital (K.M., D.B., A.P., J.C.P.K.), Department of Pharmacology and Toxicology (K.M., J.D.P.), Division of Nephrology and Obstetrical Medicine, Sunnybrook Health Sciences Centre (M.H.), and Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynaecology, Mount Sinai Hospital (J.C.P.K.), University of Toronto, Ontario, Canada.
authors.forename: Dora
authors.initials: D
authors.lastname: Baczyk
authors.affiliation: From the Division of Cardiology, Department of Medicine, Mount Sinai Hospital (K.M., J.D.P.), The Centre for Women's and Infant's Health at the Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital (K.M., D.B., A.P., J.C.P.K.), Department of Pharmacology and Toxicology (K.M., J.D.P.), Division of Nephrology and Obstetrical Medicine, Sunnybrook Health Sciences Centre (M.H.), and Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynaecology, Mount Sinai Hospital (J.C.P.K.), University of Toronto, Ontario, Canada.
authors.forename: Audrey
authors.initials: A
authors.lastname: Potts
authors.affiliation: From the Division of Cardiology, Department of Medicine, Mount Sinai Hospital (K.M., J.D.P.), The Centre for Women's and Infant's Health at the Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital (K.M., D.B., A.P., J.C.P.K.), Department of Pharmacology and Toxicology (K.M., J.D.P.), Division of Nephrology and Obstetrical Medicine, Sunnybrook Health Sciences Centre (M.H.), and Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynaecology, Mount Sinai Hospital (J.C.P.K.), University of Toronto, Ontario, Canada.
authors.forename: Michelle
authors.initials: M
authors.lastname: Hladunewich
authors.affiliation: From the Division of Cardiology, Department of Medicine, Mount Sinai Hospital (K.M., J.D.P.), The Centre for Women's and Infant's Health at the Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital (K.M., D.B., A.P., J.C.P.K.), Department of Pharmacology and Toxicology (K.M., J.D.P.), Division of Nephrology and Obstetrical Medicine, Sunnybrook Health Sciences Centre (M.H.), and Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynaecology, Mount Sinai Hospital (J.C.P.K.), University of Toronto, Ontario, Canada.
authors.forename: John D
authors.initials: JD
authors.lastname: Parker
authors.affiliation: From the Division of Cardiology, Department of Medicine, Mount Sinai Hospital (K.M., J.D.P.), The Centre for Women's and Infant's Health at the Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital (K.M., D.B., A.P., J.C.P.K.), Department of Pharmacology and Toxicology (K.M., J.D.P.), Division of Nephrology and Obstetrical Medicine, Sunnybrook Health Sciences Centre (M.H.), and Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynaecology, Mount Sinai Hospital (J.C.P.K.), University of Toronto, Ontario, Canada. jkingdom@mtsinai.on.ca.
authors.forename: John C P
authors.initials: JC
authors.lastname: Kingdom
mesh_terms: D000328:Adult; D000925:Anticoagulants / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use*; D006801:Humans; D011225:Pre-Eclampsia / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000097:blood; D012307:Risk Factors; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood
chemical_list: D000925:Anticoagulants; D015415:Biomarkers; D006495:Heparin, Low-Molecular-Weight; D011257:Pregnancy Proteins; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: PlGF; endothelium; heparin; preeclampsia; pregnancy