Back to Search
Start Over
Pravastatin prevents miscarriages in antiphospholipid antibody-treated mice.
- Source :
-
Journal of reproductive immunology [J Reprod Immunol] 2009 Nov; Vol. 82 (2), pp. 126-31. Date of Electronic Publication: 2009 Jun 24. - Publication Year :
- 2009
-
Abstract
- Miscarriages in patients with antiphospholipid (aPL) antibodies have been attributed to thrombosis of placental vessels. However, we have shown that inflammation plays a crucial role in fetal injury. We identified tissue factor (TF), the major cellular activator of the coagulation cascade, as a key mediator in inflammation and fetal injury in aPL antibody-treated mice. We found that TF in maternal neutrophils was associated with fetal injury. TF expression in neutrophils contributes to the respiratory burst and subsequent trophoblast oxidative injury and pregnancy loss induced by aPL antibodies. We also analysed how TF contributes to neutrophil activation and trophoblast injury in this model. We showed that neutrophils from aPL antibody-treated mice express protease activated receptor 2 (PAR-2) and that stimulation of this receptor leads to neutrophil activation, trophoblast injury and fetal death. Mice deficient in PAR-2 and treated with aPL antibodies exhibited reduced neutrophil activation and normal pregnancies, indicating that PAR-2 plays an important role in the pathogenesis of aPL antibody-induced fetal injury. In addition, we demonstrated that the statins simvastatin and pravastatin downregulate TF and PAR-2 expression in neutrophils and thus prevent pregnancy loss. In summary, this study shows that TF signaling through PAR-2 mediates neutrophil activation and fetal death in antiphospholipid syndrome, and that statins may be an appropriate treatment for women with aPL antibody-induced pregnancy complications.
- Subjects :
- Abortion, Habitual prevention & control
Animals
Antibodies, Antiphospholipid administration & dosage
Female
Injections, Intraperitoneal
Mice
Mice, Knockout
Mice, Transgenic
Neutrophil Activation drug effects
Neutrophil Activation genetics
Neutrophil Activation immunology
Neutrophils drug effects
Neutrophils immunology
Neutrophils pathology
Pregnancy
Receptor, PAR-2 genetics
Receptor, PAR-2 immunology
Simvastatin administration & dosage
Thromboplastin genetics
Thromboplastin immunology
Abortion, Habitual immunology
Antibodies, Antiphospholipid immunology
Neutrophils metabolism
Pravastatin administration & dosage
Receptor, PAR-2 metabolism
Thromboplastin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7603
- Volume :
- 82
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of reproductive immunology
- Publication Type :
- Academic Journal
- Accession number :
- 19556010
- Full Text :
- https://doi.org/10.1016/j.jri.2009.03.003