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. From the 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]

LEAVE A REPLY

Please enter your comment!
Please enter your name here

This site uses Akismet to reduce spam. Learn how your comment data is processed.