title: From placenta to podocyte: vascular and podocyte pathophysiology in preeclampsia.
abstract: Preeclampsia is a disorder of hypertension and proteinuria that affects 6 - 8% of normal pregnancies. Recent research has revealed many molecular mechanisms that may contribute to systemic endothelial dysfunction, glomerular capillary endotheliosis, dysregulation of the glomerular filtration apparatus, and podocyte loss. An ischemic placenta elaborates soluble FMS-like tyrosine kinase 1 (sFlt-1), a soluble receptor for vascular endothelial growth factor (VEGF). A variety of mediators, including nitric oxide, Angiotensin II receptor autoantibodies (AT1AA), and endothelin-1 may serve to maintain placental ischemia and systemic endothelial dysfunction. Endothelin-1 and decreased vascular endothelial growth factor may adversely affect overall expression and distribution of podocyte foot process proteins, leading to proteinuria. Podocyte derangements may lead to podocyte apoptosis and loss, as evidenced by the detection of live podocytes and podocyte products in the urine of preeclamptic women. In this review, we explore recent research elucidating the interactions of placenta, endothelium, and podocyte leading to the clinical syndrome of preeclampsia.
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Wagner
authors.forename: Iasmina M
authors.initials: IM
authors.lastname: Craici
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Grande
authors.forename: Vesna D
authors.initials: VD
authors.lastname: Garovic
mesh_terms: D017209:Apoptosis; D001323:Autoantibodies / Q000378:metabolism; D019332:Endothelin-1 / Q000378:metabolism; D004727:Endothelium / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007678:Kidney Glomerulus / Q000378:metabolism / Q000503:physiopathology*; D009569:Nitric Oxide / Q000378:metabolism; D010920:Placenta / Q000098:blood supply / Q000503:physiopathology*; D050199:Podocytes / Q000473:pathology / Q000502:physiology*; D011225:Pre-Eclampsia / Q000378:metabolism / Q000503:physiopathology*; D011247:Pregnancy; D011945:Receptors, Angiotensin / Q000276:immunology; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D019332:Endothelin-1; D011945:Receptors, Angiotensin; D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1