Grant: Operating Grant

Preeclampsia (PE) is a major disorder of human pregnancy, characterized by hypertension and presence of protein in the urine. The cause of PE is not well understood; however, the placenta is believed to play a central role in the development of PE. During pregnacy, placental cells invade deeply into the uterus and replace the cells on the walls of blood vessels. This results in the dilation of the vessels and an increase in the blood flow to the placenta. The initial stage of PE is caused by insufficient invasion of placental cells into the uterus, leading to the failure in dilating the blood vessels. The resulting insufficient oxygen supplies to the placenta then triggers the release of various factors into the maternal blood. These factors attack the cells lining the wall of blood vessels, leading to hypertension. MicroRNAs are tiny RNAs that have important roles in controlling which proteins are being made in cells. We have recently discovered that miR-218 levels are lower in placentas of preeclamptic patients than those of healthy women. Our preliminary data showed that miR-218 has potent effects in promoting invasion of placental cells, as well as the dilation and formation of blood vessels in the uterus. These novel findings suggest that miR-218 plays important roles in maintaining the proper placental development and transformation of blood vessels and that insufficient production of miR-218 in the placenta may contribute to the development of PE. The major objective of this grant is to investigate the role of miR-218 and its regulated cellular signalling pathways in controlling proper placenta development and how their abnormal functions may lead to PE. We will examine how miR-218 controls the ability of placental cells to invade the uterus, dilate uterine blood vessels and enhance the survival and activity of cells lining blood vessels. The proposed research will improve the understanding of PE and may reveal novel therapeutic targets for this disorder.