Abstract
Background: In preeclampsia, a hypertensive disorder of pregnancy, the poor remodeling of spiral arteries leads to placental hypoperfusion and ischemia, provoking generalized maternal endothelial dysfunction and, in severe cases, death. Endothelial and placental remodeling is important for correct pregnancy evolution and is mediated by cytokines and growth factors such as fibroblast growth factor type 2 (FGF2). In this study, we evaluated the effect of human recombinant FGF2 (rhFGF2) administration in a murine model of PE induced by NG-nitro-L-arginine methyl ester (L-NAME) to test if rhFGF2 administration can lessen the clinical manifestations of PE. Methods: Pregnant rats were administrated with 0.9% of NaCl (vehicle), L-NAME (60 mg/kg), FGF2 (666.6 ng/kg), L-NAME+FGF2 or L-NAME + hydralazine (10 mg/kg) from the 10th to 19th days of gestation. Blood pressure (BP), urine protein concentrations and anthropometric values both rat and fetuses were assessed. Histological evaluation of organs from rats delivered by cesarean section was carried out using hematoxylin and eosin staining. Results: A PE-like model was established, and it included phenotypes such as maternal hypertension, proteinuria, and fetal growth delay. Compared to the groups treated with L-NAME, the L-NAME + FGF2 group was similar to vehicle: the BP remained stable and the rats did not develop enhanced proteinuria. Both the fetuses and placentas from rats treated with L-NAME + FGF2 had similar values of weight and size compared with the vehicle. Conclusion: The intravenous administration of rhFGF2 showed beneficial and hypotensive effects, reducing the clinical manifestations of PE in the evaluated model.
Highlights
Worldwide, preeclampsia (PE), a hypertensive disorder of pregnancy, constitutes the major cause of maternal and fetal morbimortality, with an incidence of 3–10% of all pregnancies (Jeyabalan, 2013)
We evaluated the effect of human recombinant fibroblast growth factor type 2 (FGF2) administration in a murine model of PE induced by NG-nitro-L-arginine methyl ester (L-NAME) to test if rhFGF2 administration can lessen the clinical manifestations of PE
Compared to the groups treated with L-NAME, the L-NAME + FGF2 group was similar to vehicle: the Blood pressure (BP) remained stable and the rats did not develop enhanced proteinuria
Summary
Preeclampsia (PE), a hypertensive disorder of pregnancy, constitutes the major cause of maternal and fetal morbimortality, with an incidence of 3–10% of all pregnancies (Jeyabalan, 2013). The cytotrophoblast fails to remodel spiral arteries, leading to hypoperfusion and ischemia of the placenta that provoke generalized maternal endothelial dysfunction and the clinical manifestations of disease. NO serves as the main placenta vasodilatory agent, contributing to cytotrophoblast invasion, implantation, adhesion and aggregation of intervillous platelets, and placental perfusion Growth factors such as vascular endothelial growth factor (VEGF) and placental growth factor (PLGF), have the ability of regulate angiogenesis and to augment NO production and its modulation during pregnancy (Sutton et al, 2020). A hypertensive disorder of pregnancy, the poor remodeling of spiral arteries leads to placental hypoperfusion and ischemia, provoking generalized maternal endothelial dysfunction and, in severe cases, death. We evaluated the effect of human recombinant FGF2 (rhFGF2) administration in a murine model of PE induced by NG-nitro-L-arginine methyl ester (L-NAME) to test if rhFGF2 administration can lessen the clinical manifestations of PE
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