High-salt diet disturbs the physiological uterine endothelial junction remodeling during pregnancy

Abstract

A high-salt diet (HSD) induced excessive sodium intake is a major risk factor for various diseases. However, its specific effects on uterine endothelial cell and pregnancy outcomes remain poorly understood. In this study, we demonstrated that HSD induces gestation specific hypertension and adverse pregnancy outcomes in murine models. The proper spiral artery remodeling, which involved the decidual vascular endothelia, is thought to be essential for normal regulation of gestational blood pressure. We explored the molecular basis for the adaptation of vascular endothelial cell based on the transcriptome data, and uncovered the significant changes for the cell junction in the endothelia during this process. Furthermore, it was revealed that HSD induced more salt accumulation in the uteri and triggered the disturbed vascular endothelium cytoskeletal remodeling, which was associated impaired trophoblast cell invasion and incorporation into the vascular wall. Overall, our study identifies unique roles of decidual endothelium for pregnancy vascular remodeling, and demonstrates that HSD disrupts physiological spiral artery remodeling through endothelial maladaptation, which may concurrently induce systemic endothelial damage in maternal systemic vascular.