Increased placental phospholipase A gene expression and free F-isoprostane levels in response to oxidative stress in preeclampsia.

Vasoactive eicosanoids such as thromboxane (TX) A and F-isoprostanes (F-isoPs) were shown to be increased in the preeclamptic placenta. Only one of the 64 possible isomers of F-isoPs derived from the oxidation of arachidonic acid was investigated in the placenta so far. F-isoPs are released from membrane phospholipids by phospholipases A (PLA) and were shown to act on the TXA receptor (TBXA2R). However, the PLA deregulated in preeclampsia (PE) remains to be determined. In this study, we analyzed the concentrations of six isomers of F-isoPs; 8-iso-PGF, 8-iso-15(R)-PGF, 15(R)-PGF, iPF-IV, iPF-VI, 5-iPF-VI and the concentrations of the stable metabolites of TXA, TXB by high performance liquid chromatography coupled with tandem mass spectrometry in placentas of PE (n = 17) and normotensive (n = 15) pregnancies according to the biopsy site: peri-insertion or periphery. In the same biopsies, relative mRNA expression of PLA2G2A, PLA2G4A, PLA2G5, PLA2G7, the PLA2 receptor (PLA2R1), the TXA synthase and TBXAR2 were measured by quantitative RT-PCR. We observed similar concentrations of total F-isoP isomers between groups whereas higher concentrations (>40%) of free F-isoP were observed for all isomers (p ≤ 0.033) in PE than normotensive controls. As expected, we also observed higher placental concentrations of TXB in PE (p = 0.005). Interestingly, we concomitantly found higher mRNA expression of secretory PLA2G2A (p = 0.010), PLA2G5 (p = 0.038) and TBXA2R (p = 0.023) in PE than normotensive placentas. In sum, deregulated PLA could potentially be implicated in freeing F-isoP which could participate in local hypertension observed in the PE placenta through the TX pathway.