Author

Ebele Odiari

Date of Award

January 2013

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Vikki M. Abrahams

Subject Area(s)

Obstetrics and gynecology

Abstract

Women with antiphospholipid syndrome (APS) have circulating antiphospholipid antibodies (aPL) and are at risk for recurrent pregnancy loss and late pregnancy complications due placental dysfunction. Recent research has demonstrated that aPL directly alter human first trimester trophoblast function by up–regulating inflammatory cytokines, limiting cell migration, and altering angiogenic factor production. Due to their anti–inflammatory properties, Statins have been tested both in vitro, using human trophoblast, and In vivo, using a mouse model, for the treatment of APS-associated pregnancy complications and preeclampsia. In vivo mouse studies showed that statins prevent aPL–mediated fetal loss, whereas in vitro human studies suggest that statins, like pravastatin may compromise normal trophoblast function and viability. Therefore, the objective of this study was to test the hypothesis that pravastatin prevents the effects of aPL on human first trimester trophoblast function. The human first trimester trophoblast cell line, HTR8, and first trimester trophoblast primary cultures were incubated with or without an aPL in the presence or absence of pravastatin. Cytokine and angiogenic factor secretion were measured by ELISA and multiplex analysis. Cell migration was measured using a colorimetric two–chamber migration assay. Pravastatin significantly augmented the aPL–induced up–regulation of IL–8, IL–1&beta and sEndoglin secretion by HTR8 cells, but had no effect on aPL–induced up–regulation of VEGF, PlGF and GRO–&alpha. Furthermore, pravastatin alone limited basal HTR8 cell migration, and did not mitigate the adverse effect of aPL on trophoblast migration. However, Pravastatin had no effect on aPL–mediated changes in primary first trimester trophoblast function. These findings demonstrate that pravastatin does not prevent the effects of aPL antibody on first trimester trophoblast cell function, and so may not be beneficial as a therapeutic for pregnant APS patients. However, it did not have any negative effects on basal primary cell function and, therefore, may be safe to use in patients at high risk for preeclampsia.

Comments

This is an Open Access Thesis.

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