title: Placental expression profiling in preeclampsia: local overproduction of hemoglobin may drive pathological changes.
abstract: OBJECTIVE
  To create a library enriched in cDNAs from preeclamptic placentas to print onto microarrays for placental profiling of preeclampsia (PE) and high risk pregnancies.
  
  
  METHODS
  Prospective study.
  
  
  METHODS
  University women's clinic and academic research laboratory.
  
  
  METHODS
  Ten patients with PE, 5 with PE and bilateral notching, 5 with bilateral notching without PE, and 15 normotensive patients were recruited.
  
  
  METHODS
  Placenta and placenta bed biopsies were collected after delivery.
  
  
  METHODS
  Subtracted libraries of PE transcripts were produced, and cDNAs from these libraries were used to make PE-specific cDNA arrays. Results were verified quantitatively using real-time polymerase chain reaction (PCR) and histologically using in situ hybridization and immunohistochemistry.
  
  
  RESULTS
  Thirty genes were significantly altered in at least one group comparison. Differences in two candidate genes were confirmed using quantitative real-time PCR. Hemoglobin alpha2 and gamma transcripts were significantly overexpressed in the PE placenta. Scattered cells in the placenta and placental blood vessels were shown to express genes encoding these hemoglobin chains.
  
  
  CONCLUSIONS
  We demonstrate increased hemoglobin production in the PE placenta. The hemoglobin may be released into the placenta blood vessel lumen. Free heme and hemoglobin are potent toxins that cause endothelial damage and inflammation.
authors.affiliation: Department of Obstetrics and Gynecology, Lund University, Lund, Sweden. magnus.centlow@med.lu.se
authors.forename: Magnus
authors.initials: M
authors.lastname: Centlow
authors.forename: Piero
authors.initials: P
authors.lastname: Carninci
authors.forename: Krisztian
authors.initials: K
authors.lastname: Nemeth
authors.forename: Eva
authors.initials: E
authors.lastname: Mezey
authors.forename: Michael
authors.initials: M
authors.lastname: Brownstein
authors.forename: Stefan R
authors.initials: SR
authors.lastname: Hansson
mesh_terms: D001808:Blood Vessels / Q000737:chemistry / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015723:Gene Library; D006454:Hemoglobins / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D010920:Placenta / Q000098:blood supply* / Q000737:chemistry* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011225:Pre-Eclampsia / Q000235:genetics* / Q000473:pathology; D011247:Pregnancy; D011446:Prospective Studies; D012333:RNA, Messenger / Q000032:analysis; D015854:Up-Regulation
chemical_list: D006454:Hemoglobins; D012333:RNA, Messenger