Preeclampsia Hypertensive Disorders in Pregnancy
A collaboration between the Department of Obstetrics and Gynecology and the Department of Medicine at Beth Israel Deaconess Medical Center has resulted in several major breakthroughs in preeclampsia research. This research program is directed by renal specialist S. Ananth Karumanchi, M.D., HOward Highes Medical Institute Investigator and Associate Profesor in Medicine and Obstetrics and Gynecology, Harvard Medical School, who collaborates with Maternal Fetal Medicine specialists Dr. Sarosh Ranat and Dr. Kee Hack Lim. The research team has discovered key pieces of evidence to help diagnose, and eventually treat, this disease.
Overwhelming evidence points to endothelial dysfunction as the central mechanism in the pathogenesis of the maternal syndrome in preeclampsia. Dr. Karumanchi and his coworkers discovered that excess secretion of a naturally occurring antiangiogenic molecule of placental origin referred to as soluble fms-like tyrosine kinase-1 (sFlt-1)) may cause the maternal syndrome. sFlt-1 acts by antagonizing proangiogenic molecules such as vascular endothelial growth factor (VEGF) and placental growth factor (PlGF). Building on their earlier discoveries, researchers collaborated with a team from The Hospital for Sick Children, Toronto, and identified a second protein called endoglin that, in combination with sFlt1, escalates preeclampsia to a severe – and life-threatening – state. These findings were reported in June 2006 in Nature Medicine, and provided another critical piece of information about this puzzling disease. A co-receptor for transforming growth factor beta family proteins, endoglin is expressed on endothelial cells lining the blood vessels, and thereby plays an important role in maintaining the health and integrity of the vascular system. The BIDMC researchers believe that these latest findings will have important diagnostic and therapeutic implications for the diagnosis and treatment of preeclampsia. It is likely that this research will result in diagnostic tests to measure women’s levels of soluble FLT and PlGF early in pregnancy, and thus to predict whether they are likely to develop preeclampsia. Drug-based therapies for preeclampsia may still be years away, but researchers are optimistic.
These findings were published in the
New England Journal of Medicine, Nature Medicine, Journal of the American Medical Association and Journal of Clinical Investigation. They were also described in the
New Yorker Magazine. This research was funded, in part, by grants from the National Institutes of Health, the Heart and Stroke Foundation of Ontario, and by and the Department of Obstetrics and Gynecology Foundation at BIDMC. BIDMC has filed patents on methods of diagnosing and treating preeclampsia.
Finally, Dr Rana, through a K23 NIH award, is evaluating the pathogenesis of the excess cardiovascular disease noted in women with a history of preeclampsia. Dr. Rana is also a co-investigator on a multi-center randomized controlled clinical trial across several hospitals in the United States and Canada that is evaluating the role of optimal blood pressure management for patients with preeclampsia.
