Modulation of trophoblast angiogenic factor secretion by antiphospholipid antibodies is not reversed by heparin

Tamara Y. Carroll, Melissa J. Mulla, Christina S. Han, Jan J. Brosens, Larry W. Chamley, Ian Giles, Charis Pericleous, Anisur Rahman, Anna K. Sfakianaki, Michael J. Paidas, Vikki M. Abrahams

Research output: Contribution to journalArticlepeer-review

61 Scopus citations


Women with antiphospholipid antibodies (aPL) are at risk of miscarriage and pre-eclampsia, obstetrical disorders associated with reduced trophoblast invasion and spiral artery transformation. aPL target the placenta by binding beta 2-glycoprotein I (β 2GPI) on the trophoblast. In this study, we determined whether aPL alter the trophoblast secretion of angiogenic factors and evaluated the effect of low molecular weight heparin (LMWH) on this response. Method of study First-trimester trophoblast was treated with anti-β 2GPI antibodies with or without LMWH. Angiogenic factor secretion was measured by enzyme-linked immunosorbent assay. Results Trophoblast cells produced more vascular endothelial growth factor (VEGF), placenta growth factor (PlGF), and soluble endoglin following exposure to anti-β 2GPI Abs, and this occurred in both a MyD88-dependent and MyD88-independent manner. LMWH was unable to reverse the effects of the anti-β 2GPI Abs on trophoblast VEGF secretion, but enhanced PlGF. Strikingly, LMWH upregulated soluble fms-like tyrosine kinase receptor-1 (sFlt-1) secretion independently of aPL. Conclusion This study demonstrates that aPL perturb the secretion of trophoblast angiogenic factors. LMWH does not reverse this effect but exacerbates sFlt-1 secretion, a potent anti-angiogenic factor. These findings may help to explain why women with antiphospholipid syndrome, who are treated with heparin to prevent early pregnancy loss, remain at increased risk of developing late obstetrical complications, such as pre-eclampsia.

Original languageEnglish (US)
Pages (from-to)286-296
Number of pages11
JournalAmerican Journal of Reproductive Immunology
Issue number4
StatePublished - Oct 2011
Externally publishedYes


  • Angiogenic
  • Antiphospholipid
  • Placenta
  • Pregnancy
  • Trophoblast

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Reproductive Medicine
  • Obstetrics and Gynecology


Dive into the research topics of 'Modulation of trophoblast angiogenic factor secretion by antiphospholipid antibodies is not reversed by heparin'. Together they form a unique fingerprint.

Cite this