title: Evaluation of glycosaminoglycans and heparanase in placentas of women with preeclampsia.
abstract: BACKGROUND
  Preeclampsia is a multisystem disorder whose etiology remains unclear. It is already known that circulation of soluble fms-like tyrosine kinase-1 (sFlt-1) is directly involved in pre-eclampsia development. However, the molecular mechanisms involved with sFlt-1 shedding are still unidentified. We identified, quantified glycosaminoglycans and determined the enzymatic activity of heparanase in placentas of women with preeclampsia, in order to possibly explain if these compounds could be related to cellular processes involved with preeclampsia.
  
  
  METHODS
  A total of 45 samples collected from placentas, 15 samples from placentas of preeclampsia women and 30 samples from non-affected women. Heparan sulfate and dermatan sulfate were identified and quantified by agarose gel electrophoresis, whilst hyaluronic acid was quantified by an ELISA like assay. Heparanase activity was determined using biotynilated heparan sulfate as substrate.
  
  
  RESULTS
  The results showed that dermatan sulfate (P=0.019), heparan sulfate levels (P=0.015) and heparanase activity (P=0.006) in preeclampsia were significantly higher than in the control group. There was no significant difference between the groups for hyaluronic acid expression in placentas (P=0.110). The present study is the first to demonstrate directly the increase of heparan sulfate in human placentas from patients with preeclampsia, suggesting that endogenous heparan sulfate could be involved in the release of sFlt-1 from placenta, increasing the level of circulating sFlt-1.
  
  
  CONCLUSIONS
  Alterations of extracellular matrix components in placentas with preeclampsia raise the possibility that heparan sulfate released by heparanase is involved in mechanisms of preeclampsia development.
authors.affiliation: Obstetrics/Gynecology Department, Faculdade de Medicina do ABC (FMABC), São Paulo, Brazil; Biochemistry Department, Faculdade de Medicina do ABC (FMABC), São Paulo, Brazil.
authors.forename: Eduardo Augusto Brosco
authors.initials: EA
authors.lastname: Famá
authors.affiliation: Biochemistry Department, Faculdade de Medicina do ABC (FMABC), São Paulo, Brazil.
authors.forename: Renan Salvioni
authors.initials: RS
authors.lastname: Souza
authors.affiliation: Biochemistry Department, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
authors.forename: Carina Mucciolo
authors.initials: CM
authors.lastname: Melo
authors.affiliation: Obstetrics/Gynecology Department, Faculdade de Medicina do ABC (FMABC), São Paulo, Brazil.
authors.forename: Luciano
authors.initials: L
authors.lastname: Melo Pompei
authors.affiliation: Biochemistry Department, Faculdade de Medicina do ABC (FMABC), São Paulo, Brazil; Biochemistry Department, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil. Electronic address: maspinhal@yahoo.com.br.
authors.forename: Maria Aparecida Silva
authors.initials: MA
authors.lastname: Pinhal
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D005260:Female; D005966:Glucuronidase / Q000032:analysis / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D010920:Placenta / Q000737:chemistry / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000175:diagnosis* / Q000378:metabolism*; D011247:Pregnancy; D055815:Young Adult; D000099175:Heparanase
chemical_list: D005966:Glucuronidase; D006025:Glycosaminoglycans; D000099175:Heparanase
keywords: Dermatan sulfate; Heparan sulfate; Heparanase; Hyaluronic acid; Preeclampsia