title: Low molecular weight heparin modulates maternal immune response in pregnant women and mice with thrombophilia.
abstract: OBJECTIVE
  Thrombophilia is associated with pregnancy complications. Treatment with low molecular weight heparin (LMWH) improves pregnancy outcome, but the underlying mechanisms are not clear.
  
  
  METHODS
  We analyzed Treg frequency in blood from thrombophilic pregnancies treated with LMWH (n = 32) or untreated (n = 33) and from healthy pregnancies (n = 39) at all trimesters. Additionally, we treated pregnant wild-type, heterozygous and homozygous factor-V-Leiden (FVL) mice with LMWH or PBS and determined Treg frequency, pro-/anti-inflammatory cytokine levels and Caspase-3-activity in placenta and decidua.
  
  
  RESULTS
  Treg frequencies were increased in second and third trimester in LMWH-treated thrombophilic pregnancies compared to controls. Treg levels were comparable to those of normal pregnancies. Homozygous FVL mice had decreased decidual Tregs compared to wild-type mice. LMWH treatment normalized Tregs and was associated with increased decidual IL-10 mRNA. LMWH diminished Caspase-3-activity in mice of all genotypes.
  
  
  CONCLUSIONS
  We demonstrated anti-apoptotic and anti-inflammatory effects of LMWH in pregnant FVL mice. LMWH increased Treg levels in mice and humans, which suggests benefits of LMWH treatment for thrombophilic women during pregnancy.
authors.affiliation: Experimental Obstetrics and Gynecology, Medical Faculty, Otto-von-Guericke-University, Magdeburg, Germany; Department of Gynecology and Obstetrics, Medical Faculty, Otto-von-Guericke-University, Magdeburg, Germany.
authors.forename: Lydia
authors.initials: L
authors.lastname: Luley
authors.forename: Anne
authors.initials: A
authors.lastname: Schumacher
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Mulla
authors.forename: Dirk
authors.initials: D
authors.lastname: Franke
authors.forename: Michael
authors.initials: M
authors.lastname: Löttge
authors.forename: Sara
authors.initials: S
authors.lastname: Fill Malfertheiner
authors.forename: Svetlana N
authors.initials: SN
authors.lastname: Tchaikovski
authors.forename: Serban-Dan
authors.initials: SD
authors.lastname: Costa
authors.forename: Berthold
authors.initials: B
authors.lastname: Hoppe
authors.forename: Vikki M
authors.initials: VM
authors.lastname: Abrahams
authors.forename: Ana C
authors.initials: AC
authors.lastname: Zenclussen
mesh_terms: D020016:Activated Protein C Resistance / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000473:pathology; D000328:Adult; D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage*; D053148:Caspase 3 / Q000235:genetics / Q000276:immunology; D003656:Decidua / Q000276:immunology / Q000473:pathology; D005165:Factor V / Q000235:genetics / Q000276:immunology; D005260:Female; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D051379:Mice; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology
chemical_list: D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; C095381:factor V Leiden; D005165:Factor V; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3
keywords: Apoptosis; low molecular weight heparin; pregnancy; regulatory T cell; thrombophilia