High Salt Diet Causes Vascular Endothelial Dysfunction In Mice Decidua And Induces Inadequate Spiral Remodeling

High salt diet(HSD)has been confirmed poses various health risks.HSD has long existed in society and will continue to do so for a long time to come.But it has seldom reported whether high salt diet has a harmful effect on pregnant women.The main purpose of this project is to study the effects of HSD on the pregnant process.We applied mice as a long-term HSD animal model,and showed that maternal blood pressure lost physiological decent during pregnancy,boosting blood pressure,maternal high mortality after delivery,low weight and high mortality of the offspring.We proposed that a long-term salt diet has an impact on the spiral remodeling process during placental development in mice.Based on the dynamic observations,we find that anomalous spiral remodeling process appear in HSD group mice.Spiral vascular components are inadequately replaced by trophoblast cells in the HSD group,but the trophoblast cells have invasive decidual zone and surround spiral vessels.Transcriptome analysis revealed that vascular endothelium of decidual zone has dynamic changes as placental development.Importantly we note that some genes associate with cellular adhesions,junctions and cytoskeletons significantly descent from day 11 to 14 of pregnancy.We confirmed this dynamical change using tissue immunohistochemistry.In mice on the high-salt diet,endothelial junctions and adhesions remained higher than in control mice after spiral artery remodeling.We performed cellular experiments to study the mechanisms behind it.Endothelial cells can accumulate sodium under high-salt medium conditions,and the rearrangement of the cytoskeleton and the increase of tight-junction proteins between cells.Next,we applied inhibitors of sodium channels and ROCK,both of which can rescue cytoskeletal rearrangements in high-salt media.It is suggested that endothelium can accumulate sodium in a high-salt medium and rearrange the cytoskeleton via the Rho-ROCK pathway.Our study reveals that endothelial cells become loose during spiral artery remodeling in favor of trophoblast invasion.A high-salt diet can lead to an increase in maternal blood pressure during pregnancy,lower offspring weight,and a higher mortality rate among mothers.In short,HSD has a significant effect on pregnancy,leading to abnormal spiral remodeling processes,increased pregnant blood pressure and other serious pregnancy outcomes.