The LDL receptor: Traffic and function in trophoblast cells under normal and pathological conditions

During pregnancy, the developing foetus requires large amounts of cholesterol from the maternal plasma, which is mediated by proteins such as the receptor for low-density lipoproteins (LDLR). The quantity of LDLR available in the syncytiotrophoblast plasma membrane is an important factor for the uptake, metabolism, and transfer of cholesterol to foetal circulation. Because of the relevance of this receptor for cellular and systemic cholesterol metabolism in non-placental cells, the study of mechanisms associated with LDLR trafficking, such as the availability in the cell membrane, endocytosis, recycling, sorting, and degradation, have been extensively studied. Multiple protein groups are required for proper LDL/LDLR trafficking. Changes in the function of these proteins are related to hypercholesterolemia, the main risk factor associated with cardiovascular disease. It is well known that the placenta plays an essential role as a barrier between maternal lipids and the foetus and that imbalances in maternal cholesterol levels during pregnancy are frequent and associated with cardiovascular disease in the offspring. However, there is little information regarding lipoprotein trafficking in this system. In this review, we summarize the available information on LDLR trafficking, emphasizing the few reports related to receptor biology in placental cells from normal and pathological pregnancies. We conclude that extensive research on the cell biology of the placenta is required to unravel the endocytic trafficking of proteins such as LDLR in a highly specialized cell such as the syncytiotrophoblast.