The effects of pravastatin on the normal human placenta: Lessons from ex-vivo models
| Autor: | Ofer Beharier, Adelina Balan, Mahmoud Huleihel, Doron Dukler, Valeria Feinshtein, Gershon Holcberg, Shani S. Swissa, Irit Szaingurten-Solodkin |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Placental growth factor Embryology Physiology Placenta Maternal Health lcsh:Medicine Gene Expression Vascular Medicine Placental Growth Factor Endocrinology 0302 clinical medicine Pregnancy Enos Medicine and Health Sciences polycyclic compounds Medicine Phosphorylation lcsh:Science Pravastatin 030219 obstetrics & reproductive medicine Multidisciplinary biology Anticholesteremic Agents Endoglin Obstetrics and Gynecology Drugs medicine.anatomical_structure embryonic structures Female lipids (amino acids peptides and proteins) Anatomy medicine.symptom Research Article medicine.drug Placental cotyledon medicine.medical_specialty Nitric Oxide Synthase Type III In Vitro Techniques Models Biological Preeclampsia 03 medical and health sciences Growth Factors Internal medicine Humans Management of High-Risk Pregnancies Secretion Placenta Growth Factor Pharmacology Fetus Vascular Endothelial Growth Factor Receptor-1 Endocrine Physiology business.industry lcsh:R Reproductive System Statins Biology and Life Sciences nutritional and metabolic diseases Cotyledons (Anatomy) Hypoxia (medical) medicine.disease biology.organism_classification Pregnancy Complications 030104 developmental biology Vasoconstriction Women's Health lcsh:Q Physiological Processes business Developmental Biology |
| Zdroj: | PLoS ONE PLoS ONE, Vol 12, Iss 2, p e0172174 (2017) |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0172174 |
| Popis: | Introduction Research in animal models and preliminary clinical studies in humans support the use of pravastatin for the prevention of preeclampsia. However, its use during pregnancy is still controversial due to limited data about its effect on the human placenta and fetus. Methods In the present study, human placental cotyledons were perfused in the absence or presence of pravastatin in the maternal reservoir (PraM). In addition, placental explants were treated with pravastatin for 5, 24 and 72 h under normoxia and hypoxia. We monitored the secretion of placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), soluble endoglin (sEng), endothelial nitric oxide synthase (eNOS) expression and activation and the fetal vasoconstriction response to angiotensin-II. Results The concentrations of PlGF, sFlt-1 and sEng were not significantly altered by pravastatin in PraM cotyledons and in placental explants compared to control. Under hypoxic conditions, pravastatin decreased sFlt-1 concentrations. eNOS expression was significantly increased in PraM cotyledons but not in pravastatin-treated placental explants cultured under normoxia or hypoxia. eNOS phosphorylation was not significantly affected by pravastatin. The feto-placental vascular tone and the fetal vasoconstriction response to angiotensin-II, did not change following exposure of the maternal circulation to pravastatin. Conclusion We found that pravastatin does not alter the essential physiological functions of the placenta investigated in the study. The relevance of the study lays in the fact that it expands the current knowledge obtained thus far regarding the effect of the drug on the normal human placenta. This data is reassuring and important for clinicians that consider the treatment of high-risk patients with pravastatin, a treatment that exposes some normal pregnancies to the drug. |
| Databáze: | OpenAIRE |
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