title: Vitamin D reverses aPL-induced inflammation and LMWH-induced sFlt-1 release by human trophoblast.
abstract: OBJECTIVE
  Women with antiphospholipid syndrome (APS) are at increased risk of recurrent pregnancy loss (RPL) and preeclampsia. Antiphospholipid antibodies (aPL) directly alter trophoblast function. Treatment with low molecular weight heparin (LMWH) reduces the risk of RPL but not preeclampsia. Moreover, LMWH stimulates trophoblast sFlt-1 release, an anti-angiogenic factor associated with preeclampsia. Since vitamin D deficiency is associated with APS and preeclampsia, this study sought to determine the effect of vitamin D on trophoblast function in the setting of aPL and LMWH.
  
  
  METHODS
  A human first trimester trophoblast cell line (HTR8) and primary trophoblast cultures were treated with or without aPL in the presence and absence of vitamin D, LMWH or both. Trophoblast secretion of inflammatory cytokines and angiogenic factors were measured by ELISA.
  
  
  RESULTS
  Vitamin D alone or in combination with LMWH attenuated the aPL-induced trophoblast inflammatory response in the HTR8 cells and primary cultures. While vitamin D did not have any impact on aPL-mediated modulation of angiogenic factors in the primary trophoblast, it significantly inhibited LMWH-induced sFlt-1 release.
  
  
  CONCLUSIONS
  LMWH in combination with vitamin D may be more beneficial than single-agent therapy by preventing aPL-induced trophoblast inflammation and reversing LMWH-induced sFlt-1 secretion.
authors: Department of Obstetrics, Gynecology & Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA.
authors: Stefan M
authors: SM
authors: Gysler
authors: Melissa J
authors: MJ
authors: Mulla
authors: Meredith
authors: M
authors: Stuhlman
authors: Anna K
authors: AK
authors: Sfakianaki
authors: Michael J
authors: MJ
authors: Paidas
authors: Nancy L
authors: NL
authors: Stanwood
authors: Aileen
authors: A
authors: Gariepy
authors: Jan J
authors: JJ
authors: Brosens
authors: Lawrence W
authors: LW
authors: Chamley
authors: Vikki M
authors: VM
authors: Abrahams
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017152:Antibodies, Antiphospholipid / Q000276:immunology*; D002117:Calcitriol / Q000494:pharmacology*; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism*; D004353:Drug Evaluation, Preclinical; D017984:Enoxaparin / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007249:Inflammation; D016209:Interleukin-8 / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D011247:Pregnancy; D014327:Trophoblasts / Q000187:drug effects* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D017152:Antibodies, Antiphospholipid; D016207:Cytokines; D017984:Enoxaparin; D007074:Immunoglobulin G; D016209:Interleukin-8; D008565:Membrane Proteins; C098069:PIGF protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1; D002117:Calcitriol
keywords: Angiogenic; antiphospholipid antibody; inflammation; low molecular weight heparin; trophoblast; vitamin D