Document Detail


Pravastatin does not prevent antiphospholipid antibody-mediated changes in human first trimester trophoblast function.
MedLine Citation:
PMID:  22888169     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
STUDY QUESTION: What is the effect of pravastatin on antiphospholipid antibody (aPL) modulation of human first trimester trophoblast function?
SUMMARY ANSWER: 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 (β(2)GPI) 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.
MAIN FINDINGS: 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.
Authors:
Ebelechukwu A Odiari; Melissa J Mulla; Anna K Sfakianaki; Michael J Paidas; Nancy L Stanwood; Aileen Gariepy; Jan J Brosens; Larry W Chamley; Vikki M Abrahams
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-08-11
Journal Detail:
Title:  Human reproduction (Oxford, England)     Volume:  27     ISSN:  1460-2350     ISO Abbreviation:  Hum. Reprod.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-09-17     Completed Date:  2013-02-11     Revised Date:  2013-11-06    
Medline Journal Info:
Nlm Unique ID:  8701199     Medline TA:  Hum Reprod     Country:  England    
Other Details:
Languages:  eng     Pagination:  2933-40     Citation Subset:  IM    
Affiliation:
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06510, USA.
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MeSH Terms
Descriptor/Qualifier:
Angiogenesis Inducing Agents / metabolism
Antibodies, Antiphospholipid / immunology
Antibodies, Monoclonal
Antiphospholipid Syndrome / drug therapy,  immunology*
Cell Line
Cell Movement / drug effects
Cytokines / secretion
Enzyme-Linked Immunosorbent Assay
Humans
Multiplex Polymerase Chain Reaction
Pravastatin / pharmacology*
Trophoblasts / drug effects*,  immunology,  pathology
beta 2-Glycoprotein I / immunology
Chemical
Reg. No./Substance:
0/Angiogenesis Inducing Agents; 0/Antibodies, Antiphospholipid; 0/Antibodies, Monoclonal; 0/Cytokines; 0/beta 2-Glycoprotein I; 81093-37-0/Pravastatin

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