
March 2003 From Journal of Clinical Investigation The elusive preeclampsia factor discovered? Eclampsia, the occurrence of often fatal seizures during pregnancy, is preceded by a condition called preeclampsia. Preeclampsia itself is a serious complication of pregnancy and affects up to 5% of pregnant women. Diagnosed in its early stages by elevated blood pressure and protein levels in the urine, it is the major cause of premature birth and perinatal child death and accounts for approximately 15% of all maternal deaths. Despite decades of intensive research, we still do not know what causes preeclampsia.In preeclamptic women, blood flow to the placenta is reduced, and the supply of oxygen is decreased. Low placental oxygen levels have been proposed to trigger the release of unknown factors in the placenta that mediate a rapid and unpredictable progression to numerous multisystem complications involving the maternal liver, kidneys, lungs, blood and nervous systems. Two articles in the March 3 issue of the Journal of Clinical Investigation now shed new light on the pathophysiology of this disease. In the first article, S. Ananth Karumanchi and colleagues at Beth Israel Deaconess Medical Center in Boston report that preeclampsia is associated with elevated levels of a protein called sFlt1. To test whether sFlt1 is responsible for the problems in women with preeclampsia, the scientists treated pregnant and non-pregnant rats with this protein. Irrespective of pregnancy, the exposed rats exhibited several of the hallmark clinical and pathological features of preeclampsia, providing a strong argument for a causal role for sFlt1. sFlt1 binds to and "mops up" a group of proteins--called angiogenic factors--which promote the growth of new blood vessels and are involved in maintenance of the adult vasculature. Elevated levels of sFlt1 presumably reduce the circulating levels of angiogenic factors, such as vascular endothelial growth factor (VEGF) and placental growth factor, below a threshold necessary for integrity of the mother's blood vessels. A compromised vascular system could explain many of the symptoms of preeclampsia. In the second article, Susan Quaggin and colleagues of the Samuel Lunenfeld Research Institute in Toronto, report that reducing the levels of one particular angiogenic factor (called VEGF-A) in a subset of kidney cells in mice causes kidney disease very similar to that seen in women with preeclampsia. Taken together, as discussed in an accompanying commentary by Peter Carmeliet and Aernout Luttun (of Katholieke Universiteit Leuven, Belgium), these results suggest a plausible scenario of what goes wrong during preeclampsia, and point to molecules and molecular pathways that are potential targets for therapeutic intervention. CONTACT: Ananth Karumanchi Beth Israel Deaconess Medical Center 330 Brookline Avenue Dana 517, Renal Division Boston, MA 02215 USA Phone 1: 617-667-1018 Fax 1: 617-667-7581 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/17189.pdf CONTACT: Susan Quaggin Mount Sinai Hospital The Samuel Lunenfeld Research Institute Rm. #871Q 600 University Ave. Toronto, ON M5G 1X5 CANADA Phone: 416-586-4800 Fax: 416-586-8588 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/17423.pdf ACCOMPANYING COMMENTARY: Soluble VEGF receptor Flt1: the elusive preeclampsia factor discovered? CONTACT: Peter Carmeliet KU Leuven Flanders Interuniversity Institute of Biotechnology Center For Transgene Technology & Gene Therapy Campus Gasthuisberg, Herestraat 49 Leuven, B-3000 BELGIUM Phone 1: 32-16-345-772 Phone 2: 32-16-34-57-80 Fax 1: 32-16-345-990 E-mail: [email protected] View the PDF of this commentary at: https://www.the-jci.org/press/18015.pdf **Please mention the Journal of Clinical Investigation as the source of these articles** |