Pravastatin does not prevent antiphospholipid antibody-mediated changes in human first trimester trophoblast function
Authors: Odiari, Ebelechukwu A.; Mulla, Melissa J.; Sfakianaki, Anna K.; Paidas, Michael J.; Stanwood, Nancy L.; Gariepy, Aileen; Brosens, Jan J.; Chamley, Larry W.; Abrahams, Vikki M.
Source: Human Reproduction, Volume 27, Number 10, 18 October 2012 , pp. 2933-2940(8)
Publisher: Oxford University Press
What is the effect of pravastatin on antiphospholipid antibody (aPL) modulation of human first trimester trophoblast function?
Pravastatin does not prevent the effects of aPL on human first trimester trophoblast cell function.
WHAT IS KNOWN ALREADY
Antiphospholipid syndrome (APS) is associated with recurrent pregnancy loss and late pregnancy complications, such as pre-eclampsia, owing to direct targeting of the placenta by aPL. While treatment with heparin reduces the rate of pregnancy loss, the risk for severe pre-eclampsia remains high. Thus, there is a need to find alternative treatments for the prenatal management of patients with APS. Statins have recently been shown to prevent aPL-mediated fetal loss in mice but their effects on a human pregnancy model of APS have not yet been studied.
DESIGN, DATA COLLECTION, METHODS
The human first trimester trophoblast cell line, HTR8, and human first trimester trophoblast primary cultures were incubated with or without a mouse anti-human beta 2 glycoprotein I (β2GPI) monoclonal antibody in the presence or absence of pravastatin. Cytokine and angiogenic factor secretion were measured by enzyme-linked immunosorbent assay and multiplex analysis. Cell migration was measured using a colorimetric two-chamber migration assay.
Using the human first trimester trophoblast cell line, HTR8, pravastatin significantly augmented, compared with no treatment, aPL-dependent secretion of interleukin (IL)-8 (P< 0.05), IL-1β (P< 0.05) and soluble endoglin (P< 0.01) but had no effect on aPL-induced up-regulation of vascular endothelial growth factor, placenta growth factor or growth-related oncogene alpha secretion. Furthermore, pravastatin alone limited basal HTR8 cell migration (P< 0.01), and did not mitigate the adverse effect of aPL on trophoblast migration. Pravastatin also had no impact on the secretion of pro-inflammatory cytokines and angiogenic factors by primary human first trimester trophoblast cells exposed to aPL.
LIMITATIONS AND WIDER IMPLICATIONS OF THE FINDINGS
While our in vitro findings suggest that pravastatin may not be effective in preventing pregnancy complications in patients with APS, the in vivo condition may be more complex, and thus, more studies are needed to determine the effectiveness of pravastatin in the prevention of aPL-associated pregnancy complications in humans.
STUDY FUNDING/COMPETING INTEREST(S)
This work was supported by the American Heart Association.
Document Type: Research Article
Publication date: 2012-10-18
- Human Reproduction features full-length, peer-reviewed papers reporting original research, clinical case histories, as well as opinions and debates on topical issues. Papers published cover the scientific and medical aspects of reproductive physiology and pathology, endocrinology, andrology, gonad function, gametogenesis, fertilization, embryo development, implantation, pregnancy, genetics, genetic diagnosis, oncology, infectious disease, surgery, contraception, infertility treatment, psychology, ethics and social issues. The highest scientific and editorial standard is maintained throughout the journal along with a rapid rate of publication.
- In this: publication
- By this: publisher
- In this Subject: Anatomy & Physiology , Obstetrics & Gynecology
- By this author: Odiari, Ebelechukwu A. ; Mulla, Melissa J. ; Sfakianaki, Anna K. ; Paidas, Michael J. ; Stanwood, Nancy L. ; Gariepy, Aileen ; Brosens, Jan J. ; Chamley, Larry W. ; Abrahams, Vikki M.