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Vitamin D reverses aPL-induced inflammation and LMWH-induced sFlt-1 release by human trophoblast

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Gysler, Stefan M., Mulla, Melissa J., Stuhlman, Meredith, Sfakianaki, Anna K., Paidas, Michael J., Stanwood, Nancy L., Gariepy, Aileen, Brosens, Jan J., Chamley, Lawrence W. and Abrahams, Vikki M. (2014) Vitamin D reverses aPL-induced inflammation and LMWH-induced sFlt-1 release by human trophoblast. American Journal of Reproductive Immunology . n/a-n/a. doi:10.1111/aji.12301 ISSN 1046-7408.

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Official URL: http://dx.doi.org/10.1111/aji.12301

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Abstract

Problem
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.

Method of study
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.

Conclusion
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.

Item Type: Journal Article
Divisions: Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Reproductive Health ( - until July 2016)
Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Journal or Publication Title: American Journal of Reproductive Immunology
Publisher: Wiley-Blackwell Publishing, Inc.
ISSN: 1046-7408
Official Date: 29 July 2014
Dates:
DateEvent
29 July 2014Published
7 July 2014Accepted
10 June 2014Submitted
Page Range: n/a-n/a
DOI: 10.1111/aji.12301
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Restricted or Subscription Access

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