{"id":{"repo_id":"toronto-retro","oai_identifier":"oai:utoronto.scholaris.ca:1807/105842"},"canonical_url":"https://search.dev.ndltd.org/etd/toronto-retro/oai:utoronto.scholaris.ca:1807/105842","repository":{"repo_id":"toronto-retro","name":"University of Toronto","base_url":"https://utoronto.scholaris.ca/server/oai/request"},"display":{"title":"Vascular Effects of Low-Molecular Weight Heparin in Pregnant Women at High-Risk of Preeclampsia","abstract":"Preeclampsia (PE) is a hypertensive disorder of pregnancy characterized by new-onset hypertension with evidence of organ injury. Women with severe PE demonstrate cardiovascular impairment during pregnancy and are at higher risk of cardiovascular disease postpartum. There is currently no effective therapy for the prevention of PE in high-risk pregnant women. Low-molecular weight heparin (LMWH) has been investigated for the prevention of severe PE, although the underlying mechanisms of action are unknown. The objective of the first experiment was to assess cardiovascular function in pregnant women at high-risk of PE compared with low-risk pregnant controls at 24 weeksâ gestation. High-risk women demonstrated a lower cardiac output, higher resistance hemodynamic profile with impaired radial artery flow-mediated dilation (FMD), compared to controls. Baseline plasma and urine levels of placental growth factor (PlGF) were significantly lower in high-risk women compared with controls. These findings demonstrate that pregnant women at high-risk of PE exhibit impaired endothelial function prior to the clinical presentation of PE. The acute cardiovascular effects of LMWH in pregnant women at high-risk of PE were then investigated. LMWH significantly increased FMD in high-risk women and maternal plasma levels of PlGF, suggesting that LMWH may exert beneficial effects on maternal endothelial function. To further elucidate the effects of LMWH on the maternal endothelium, the effects of patient serum and LMWH on in vitro endothelial cell function were investigated. Serum from high-risk women impaired angiogenesis and increased PlGF-1 and PlGF-2 expression compared to serum from low-risk subjects. Co-exposure of high-risk serum with LMWH improved the angiogenic response, such that it was equivalent to that of low-risk serum, and promoted PlGF secretion from endothelial cells. These observations provide further evidence that LMWH modifies endothelial cell function, possibly through enhanced PlGF bioavailability. In conclusion, the present experiments indicate that LMWH improves endothelial function in pregnant women at high-risk of developing PE, possibly mediated through increased PlGF bioavailability. These findings are consistent with previous clinical studies in non-pregnant populations and animal studies in which LMWH improved endothelial function. Future trials are needed to assess the effectiveness of LMWH for the prevention of severe PE in high-risk women.","abstract_html":"Preeclampsia (PE) is a hypertensive disorder of pregnancy characterized by new-onset hypertension with evidence of organ injury. Women with severe PE demonstrate cardiovascular impairment during pregnancy and are at higher risk of cardiovascular disease postpartum. There is currently no effective therapy for the prevention of PE in high-risk pregnant women. Low-molecular weight heparin (LMWH) has been investigated for the prevention of severe PE, although the underlying mechanisms of action are unknown. The objective of the first experiment was to assess cardiovascular function in pregnant women at high-risk of PE compared with low-risk pregnant controls at 24 weeksâ gestation. High-risk women demonstrated a lower cardiac output, higher resistance hemodynamic profile with impaired radial artery flow-mediated dilation (FMD), compared to controls. Baseline plasma and urine levels of placental growth factor (PlGF) were significantly lower in high-risk women compared with controls. These findings demonstrate that pregnant women at high-risk of PE exhibit impaired endothelial function prior to the clinical presentation of PE. The acute cardiovascular effects of LMWH in pregnant women at high-risk of PE were then investigated. LMWH significantly increased FMD in high-risk women and maternal plasma levels of PlGF, suggesting that LMWH may exert beneficial effects on maternal endothelial function. To further elucidate the effects of LMWH on the maternal endothelium, the effects of patient serum and LMWH on in vitro endothelial cell function were investigated. Serum from high-risk women impaired angiogenesis and increased PlGF-1 and PlGF-2 expression compared to serum from low-risk subjects. Co-exposure of high-risk serum with LMWH improved the angiogenic response, such that it was equivalent to that of low-risk serum, and promoted PlGF secretion from endothelial cells. These observations provide further evidence that LMWH modifies endothelial cell function, possibly through enhanced PlGF bioavailability. In conclusion, the present experiments indicate that LMWH improves endothelial function in pregnant women at high-risk of developing PE, possibly mediated through increased PlGF bioavailability. These findings are consistent with previous clinical studies in non-pregnant populations and animal studies in which LMWH improved endothelial function. Future trials are needed to assess the effectiveness of LMWH for the prevention of severe PE in high-risk women.","abstract_has_math":false,"creators":["McLaughlin, Kelsey"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":"Pharmacology","school":null,"contributors":[],"advisors":["Parker, John D","Kingdom, John CP"],"committee_chairs":[],"committee_members":[],"year":2017,"date_issued":"2017-06","date_published":"2017-06","updated_at":"2026-07-27T21:27:52Z","subjects":[],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/1807/105842","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Parker, John D","Kingdom, John CP"]},{"key":"dc:contributor.department","label":"Department","values":["Pharmacology"]},{"key":"dc:creator","label":"Author","values":["McLaughlin, Kelsey"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2017-06"]},{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2021-06-01T04:00:09Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2021-06-01T04:00:09Z"]},{"key":"dc:date.issued","label":"Date","values":["2017-06"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/1807/105842"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Preeclampsia (PE) is a hypertensive disorder of pregnancy characterized by new-onset hypertension with evidence of organ injury. Women with severe PE demonstrate cardiovascular impairment during pregnancy and are at higher risk of cardiovascular disease postpartum. There is currently no effective therapy for the prevention of PE in high-risk pregnant women. Low-molecular weight heparin (LMWH) has been investigated for the prevention of severe PE, although the underlying mechanisms of action are unknown. The objective of the first experiment was to assess cardiovascular function in pregnant women at high-risk of PE compared with low-risk pregnant controls at 24 weeksâ gestation. High-risk women demonstrated a lower cardiac output, higher resistance hemodynamic profile with impaired radial artery flow-mediated dilation (FMD), compared to controls. Baseline plasma and urine levels of placental growth factor (PlGF) were significantly lower in high-risk women compared with controls. These findings demonstrate that pregnant women at high-risk of PE exhibit impaired endothelial function prior to the clinical presentation of PE. The acute cardiovascular effects of LMWH in pregnant women at high-risk of PE were then investigated. LMWH significantly increased FMD in high-risk women and maternal plasma levels of PlGF, suggesting that LMWH may exert beneficial effects on maternal endothelial function. To further elucidate the effects of LMWH on the maternal endothelium, the effects of patient serum and LMWH on in vitro endothelial cell function were investigated. Serum from high-risk women impaired angiogenesis and increased PlGF-1 and PlGF-2 expression compared to serum from low-risk subjects. Co-exposure of high-risk serum with LMWH improved the angiogenic response, such that it was equivalent to that of low-risk serum, and promoted PlGF secretion from endothelial cells. These observations provide further evidence that LMWH modifies endothelial cell function, possibly through enhanced PlGF bioavailability. In conclusion, the present experiments indicate that LMWH improves endothelial function in pregnant women at high-risk of developing PE, possibly mediated through increased PlGF bioavailability. These findings are consistent with previous clinical studies in non-pregnant populations and animal studies in which LMWH improved endothelial function. Future trials are needed to assess the effectiveness of LMWH for the prevention of severe PE in high-risk women."]},{"key":"dc:description.degree","label":"Dc Description Degree","values":["Ph.D."]},{"key":"dc:title","label":"Title","values":["Vascular Effects of Low-Molecular Weight Heparin in Pregnant Women at High-Risk of Preeclampsia"]}]}],"canonical_facts":{"dc:contributor.advisor":["Parker, John D","Kingdom, John CP"],"dc:contributor.department":["Pharmacology"],"dc:creator":["McLaughlin, Kelsey"],"dc:date":["2017-06"],"dc:date.accessioned":["2021-06-01T04:00:09Z"],"dc:date.available":["2021-06-01T04:00:09Z"],"dc:date.issued":["2017-06"],"dc:description.abstract":["Preeclampsia (PE) is a hypertensive disorder of pregnancy characterized by new-onset hypertension with evidence of organ injury. Women with severe PE demonstrate cardiovascular impairment during pregnancy and are at higher risk of cardiovascular disease postpartum. There is currently no effective therapy for the prevention of PE in high-risk pregnant women. Low-molecular weight heparin (LMWH) has been investigated for the prevention of severe PE, although the underlying mechanisms of action are unknown. The objective of the first experiment was to assess cardiovascular function in pregnant women at high-risk of PE compared with low-risk pregnant controls at 24 weeksâ gestation. High-risk women demonstrated a lower cardiac output, higher resistance hemodynamic profile with impaired radial artery flow-mediated dilation (FMD), compared to controls. Baseline plasma and urine levels of placental growth factor (PlGF) were significantly lower in high-risk women compared with controls. These findings demonstrate that pregnant women at high-risk of PE exhibit impaired endothelial function prior to the clinical presentation of PE. The acute cardiovascular effects of LMWH in pregnant women at high-risk of PE were then investigated. LMWH significantly increased FMD in high-risk women and maternal plasma levels of PlGF, suggesting that LMWH may exert beneficial effects on maternal endothelial function. To further elucidate the effects of LMWH on the maternal endothelium, the effects of patient serum and LMWH on in vitro endothelial cell function were investigated. Serum from high-risk women impaired angiogenesis and increased PlGF-1 and PlGF-2 expression compared to serum from low-risk subjects. Co-exposure of high-risk serum with LMWH improved the angiogenic response, such that it was equivalent to that of low-risk serum, and promoted PlGF secretion from endothelial cells. These observations provide further evidence that LMWH modifies endothelial cell function, possibly through enhanced PlGF bioavailability. In conclusion, the present experiments indicate that LMWH improves endothelial function in pregnant women at high-risk of developing PE, possibly mediated through increased PlGF bioavailability. These findings are consistent with previous clinical studies in non-pregnant populations and animal studies in which LMWH improved endothelial function. Future trials are needed to assess the effectiveness of LMWH for the prevention of severe PE in high-risk women."],"dc:description.degree":["Ph.D."],"dc:identifier.uri":["http://hdl.handle.net/1807/105842"],"dc:title":["Vascular Effects of Low-Molecular Weight Heparin in Pregnant Women at High-Risk of Preeclampsia"],"dc:type":["Thesis"]},"updated_at":"2026-07-27T21:27:52Z"}