Grant: Project Grant

Preeclampsia (PE) is a major disorder of human pregnancy, characterized by high blood pressure and presence of proteins in the urine. PE is not only the leading cause of maternal death and still birth, but also affects the health of mothers and children later in their lives. The cause of PE is not well understood; however, insufficient invasion of placental cells into the uterus and subsequent failure to modify uterine blood vessels is thought to be the initial event of PE. This results in insufficient blood supplies to the placenta, causing an abnormal secretion of factors from the placenta into the blood to affect the functions of cells lining the blood vessels, known as endothelial cells. MicroRNAs are tiny RNAs that have important roles in controlling the levels of proteins being made in cells. We have recently discovered that miR-218 levels are lower in placentas of PE patients than those of healthy women. Our preliminary data showed that miR-218 has potent effects in promoting invasion of placental cells to the uterus and to dilate the maternal blood vessels. We also found that miR-218 may regulate the function of endothelial cells. These novel findings suggest that miR-218 plays important roles in maintaining the proper development of the placenta and that insufficient production of miR-218 in the placenta contributes to the development of PE. The major objectives of this grant are to further investigate the role of miR-218 in placenta development; to identify which key molecules are regulated by miR-218; and to determine how abnormal production of miR-218 may lead to PE. We will use cells derived from placenta, placental organ culture and placenta/uterus co-culture systems, as well as endothelial cells, to study the functions of miR-218 and the key molecules regulated by miR-218. The proposed research will improve the understanding of PE and may reveal novel diagnostic and therapeutic targets for this disorder.