Preeclampsia remains one of the most feared complications of pregnancy: it affects between 2.7% and 8.2% of pregnant women and manifests, after the twentieth week, as arterial hypertension (systolic pressure greater than or equal to 140 mm Hg, or diastolic pressure greater than or equal to 90 mm Hg) associated with proteinuria. This condition increases the risk of preterm birth, cardiovascular disease, and kidney disease in the mother, and may lead to the death of both mother and fetus. Its origin is attributed to defective invasion of extravillous trophoblasts into the uterine endometrium and to incomplete remodeling of the uterine spiral arteries, a process that occurs around the eighth to tenth week of pregnancy. Insufficient trophoblast invasion gives rise to diffuse inflammation and endothelial dysfunction, notably including increased platelet aggregation and placental infarcts, within a context of imbalance between angiogenic and anti-angiogenic factors.
Options for early intervention remain limited. The standard strategy relies on prolonged administration of low-dose aspirin, which inactivates cyclooxygenase-1 and reduces the production of prostaglandins and thromboxane. However, this approach fails to correct placental lesions: it improves neither the concentrations of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt1), nor placental blood perfusion. The search for alternative molecules therefore appears essential. A previous systematic assessment had identified 153 candidates, a few of which were judged to have high or medium potential, including metformin and certain statins, already explored in clinical trials.
In this literature review, the authors propose to evaluate rosiglitazone, a synthetic agonist of the peroxisome proliferator-activated receptor gamma (PPARγ), as a candidate for early intervention. Unlike approaches aimed solely at mitigating damage, this molecule is already used in humans. The authors summarize the mechanisms involving PPARγ in preeclampsia documented over recent decades and examine the toxicity as well as the practical outcomes of rosiglitazone in the clinical setting. The cited studies suggest in particular that PPARγ activation by rosiglitazone restores the expression of heme oxygenase-1 in the preeclamptic placenta, enhances the antioxidant response of human trophoblast, and prevents apoptosis, while several observations report pregnancies carried to term following inadvertent exposure to the molecule.
By bringing together these mechanistic and clinical data, this review argues in favor of the feasibility of clinical trials designed to test rosiglitazone in the treatment of preeclampsia.