Miss Adelina Balan1, Mrs. Shani S. Swissa1, Irit Szaingurten-Solodkin Ph.D.1, Valeria Feinshtein Ph.D.2, Mahmoud Huleihel Ph.D. 3, Gershon Holcberg M.D.4 and Ofer Beharier M.D. Ph.D.1,4
1Department of Physiology and Cell Biology, 2Department of Clinical Biochemistry and Pharmacology, 3The Shraga Segal Department of Microbiology and Immunology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel. 4Department of Obstetrics and Gynecology, Soroka University Medical Center and Ben-Gurion University of the Negev, Beer Sheva, Israel.
Introduction: Extensive research in animal models marked pravastatin as a treatment to eliminate preeclampsia. However, the effect of the drug on human tissue is extremely limited. Our study focuses on the secretion of angiogenic factors, inflammatory cytokines and nitric oxide (NO) in the human placenta following pravastatin exposure.
Methods: placental cotyledons were perfused in the absence (Cntl) or presence of pravastatin in the maternal reservoir (PraM) or the maternal and fetal reservoirs (PraMF). The concentrations of placental growth factor (PlGF), soluble Fms-like tyrosine kinase-1 (sFlt-1), soluble endoglin (sEng), tumor necrosis factor-a (TNF-a), interleukin (IL)-6 and IL-10 were measured by ELISA. Endothelial NO synthase (eNOS) expression in the placenta, was determined by immunoblot analysis. The concentrations of NO were determined by measurements of nitrite.
Results: PraM exposure did not alter PlGF, sFlt-1, sEng, TNF-a, IL-6 and IL-10 secretion, compared to Cntl. However, PraMF exposure significantly increased the secretion of sFlt-1 and IL-6 to the maternal circulation and IL-10 to the feral circulation. Both PraM and PraMF induced a significant increase in eNOS expression. Nevertheless, increased NO secretion to the maternal circulation was induced only in response to PraMF and the secretion to the fetal circulation, did not differ at all.
Conclusions: In the normal human placenta, maternal exposure to pravastatin does not change the secretion of angiogenic factors, inflammatory cytokines and NO. In contrast, maternal and fetal exposure to pravastatin initiates anti-angiogenic and pro-inflammatory reactions along with increased NO secretion.