title: Tumor necrosis factor α induces a model of preeclampsia in pregnant baboons (Papio hamadryas).
abstract: Preeclampsia is a common disease of pregnancy characterised by maternal hypertension and proteinuria. Abnormal placentation in early pregnancy and abnormal cytokine and anti-angiogenic factor expression are thought to contribute to the clinical syndrome of endothelial dysfunction evident in the second half of gestation. The mechanisms underlying both the placental pathology and its translation to the maternal clinical syndrome are not fully understood. A model of preeclampsia manifest by clinically evident endothelial dysfunction (increased blood pressure and proteinuria) was induced by administration of low-dose TNF-α for 2weeks at mid-gestation in pregnant baboons (Papio hamadryas). Blood pressure was monitored continuously and remotely by intra-arterial radiotelemetry. Following TNF-α infusion, there was an increase in systolic and diastolic blood pressure and development of proteinuria in pregnant treated animals, but not in pregnant saline controls nor in non-pregnant TNF-α treated animals. The treated pregnant animals also developed elevated plasma soluble FMS-like tyrosine kinase-1 (sFLT-1) and increased placental mRNA expression of sFLT-1 and soluble endoglin (sEng). These results clearly demonstrate that the cytokine TNF-α can induce the clinical and biochemical features of human preeclampsia. The results identify a link between cytokines, placental dysfunction and endothelial dysfunction resulting in a loss of maternal blood pressure control.
authors: Vascular Immunology Laboratory, The Heart Research Institute, Newtown, New South Wales, Australia. neroli_sunderland@hotmail.com
authors: Neroli S
authors: NS
authors: Sunderland
authors: Sally E
authors: SE
authors: Thomson
authors: Scott J
authors: SJ
authors: Heffernan
authors: Shirlene
authors: S
authors: Lim
authors: John
authors: J
authors: Thompson
authors: Robert
authors: R
authors: Ogle
authors: Paul
authors: P
authors: McKenzie
authors: Paul J
authors: PJ
authors: Kirwan
authors: Angela
authors: A
authors: Makris
authors: Annemarie
authors: A
authors: Hennessy
mesh_terms: D000818:Animals; D001483:Base Sequence; D001794:Blood Pressure; D001798:Blood Proteins / Q000032:analysis; D017931:DNA Primers; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D010215:Papio; D010920:Placenta / Q000378:metabolism; D011225:Pre-Eclampsia / Q000139:chemically induced* / Q000503:physiopathology; D011247:Pregnancy; D011507:Proteinuria / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013686:Telemetry; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage*
chemical_list: D001798:Blood Proteins; D017931:DNA Primers; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha