Disruption of LDL receptor trafficking in placentas from maternal supraphysiological hypercholesterolemia: A study of key endocytosis and recycling proteins

Introduction: During pregnancy, some women experience elevated cholesterol levels, known as maternal supraphysiological hypercholesterolemia (MSPH), which can cause oxidative stress and endothelial dysfunction in the fetus. Although cholesterol levels in newborns of MSPH mothers do not differ from those of mothers with physiological hypercholesterolemia (MPH), cholesterol transport through the placenta is affected. This study examines proteins involved in the endocytosis and recycling of the low-density lipoprotein receptor (LDLR) in MSPH placentas, highlighting alterations in LDLR localization and function which associates with modulation of maternal-to fetal cholesterol traffic. Methods: Maternal serum samples and placental tissue samples (n = 23) were used. Mothers were classified into MPH and MSPH groups according to their cholesterol levels. The concentrations and localizations of proteins involved in LDL recycling, such as adaptins α and β, transgelin, blos-1, CCD93, clathrin, PCSK9, SNX17, and LDLR, were measured via western blot and immunofluorescence. In addition, LDLR gene expression was assessed by qPCR. Differences between groups were determined via Student's t-test. p < 0.05 was considered significant. Results: Our results show LDLR distributed mainly in the surface of the syncytiotrophoblast without changes in its total amount. Additionally, an increase in PCSK9 and a reduction in SNX17 was described in MSPH placentas. Conclusions: In conclusion, our results show that the placenta express proteins required for a proper LDLR endocytosis and recycling and suggest alterations in proteins associated with LDL trafficking in the MSPH placenta, which could respond to elevated maternal cholesterol levels and regulate the maternal-to-fetal cholesterol traffic.