Vitamin D Reverses aPL ‐induced Inflammation and LMWH‐induced s F lt‐1 Release by Human Trophoblast

Problem Women with antiphospholipid syndrome ( APS ) are at increased risk of recurrent pregnancy loss ( RPL ) and preeclampsia. Antiphospholipid antibodies (a PL ) directly alter trophoblast function. Treatment with low molecular weight heparin ( LMWH ) reduces the risk of RPL but not preeclampsia. Moreover, LMWH stimulates trophoblast sF lt‐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 a PL and LMWH . Method of study A human first trimester trophoblast cell line ( HTR 8) and primary trophoblast cultures were treated with or without a PL 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 HTR 8 cells and primary cultures. While vitamin D did not have any impact on a PL ‐mediated modulation of angiogenic factors in the primary trophoblast, it significantly inhibited LMWH ‐induced s F lt‐1 release. Conclusion LMWH in combination with vitamin D may be more beneficial than single‐agent therapy by preventing a PL ‐induced trophoblast inflammation and reversing LMWH ‐induced s F lt‐1 secretion.