Abstract
Preeclampsia is a pregnancy complication characterized by the new onset of hypertension and proteinuria at 20 weeks of gestation or later that may also present without proteinuria but with evidence of systemic disease, such as thrombocytopenia or elevated levels of liver transaminases. This multisystem disorder targets several organs, most often the kidneys, liver, and brain, constituting the leading cause of maternal and perinatal morbidity and mortality, with an estimated incidence of 2% to 8% on all pregnancies. Many studies have focused their attention on preeclampsia; nevertheless, the disease’s etiology and its associated molecular pathways are not completely understood. 1 –6
Aspirin is currently the most commonly used prophylaxis treatment for pregnant women at risk of preeclampsia. Although several other pharmacological drugs showed promising effects on preeclampsia prevention, aspirin is still the only drug with enough clinical trials and substantial evidence supporting its efficacy. 7 –10 Despite this, the molecular targets of aspirin in the fight against preeclampsia are not completely understood. On the other hand, peroxisome proliferator-activated receptors (PPARs), which are ligand-activated transcription factors acting as important regulators of cell differentiation and proliferation, have been shown to play a major role in the pathogenesis of preeclampsia, particularly PPARγ. 11 Interestingly, the effects of aspirin on PPARγ in patients with preeclampsia have never been investigated before. In the current issue of Reproductive Sciences, Zhang and colleagues aimed to fill in this knowledge gap by determining whether aspirin could attenuate PPARγ inhibitor (T0070907)-induced preeclampsia and its impact on PPARγ expression. 12
In order to reach their aim, Zhang et al treated 60 rats with different doses of aspirin in the presence or absence of T0070907. The authors observed that the T007097-exposed rats presented with a significant decrease in the fetal weight and an increase in the placental weight, as compared to the controls and as expected. When these mice were treated with aspirin, their mean arterial blood pressure was significantly reduced. Moreover, treatment with 1.5 mg/kg of aspirin showed it to be successful in reversing the effects of the PPARγ inhibitor. In addition, aspirin treatment reversed the T0070907-induced changes in the levels of thromboxane B2, vascular endothelial growth factor, soluble fms-like tyrosine kinase, and matrix metalloproteinase 2 in both maternal blood and placental tissue. Zhang and colleagues also observed that the PPARγ inhibitor-induced increase in messenger RNA and protein levels of Cox1 and Cox2 was markedly reduced by aspirin treatment. Finally, the authors were able to demonstrate that T0070907 repressed both the transcriptional and translational levels of PPARγ and that these actions were reversed with aspirin treatment. 12
In sum, the work presented by Zhang et al further confirms the successful action of aspirin in counteracting preeclampsia, highlighting the role of PPARγ in the development of the condition.