The test results showed that a protein known as soluble fms-like tyrosine kinase 1 (sFlt1) was significantly elevated among the preeclampsia patients. With this information in hand, the researchers administered the protein to both pregnant and non-pregnant rats to test whether sFlt1 was at the root of the problem.
"The resulting data was exciting," says Karumanchi. "The rats that were exposed to sFlt1 had distinct clinical and pathological symptoms of preeclampsia, demonstrating for the first time a clear cause and effect relationship between this protein and this disease."
What is apparently happening, he explains, is that sFlt1 is binding to and "mopping up" another group of proteins, known as angiogenic factors. "Vascular endothelial growth factor (VEGF) and placental growth factor (PIGF) exist to promote angiogenesis, the growth and health of small blood vessels," he explains. VEGF has, in fact, been shown to promote tumor growth among cancer patients and is therefore the target of anti-angiogenic therapies being developed for the treatment of some malignancies.
Among preeclampsia patients, says Karumanchi, the diminished levels of VEGF and PIGF caused by the actions of sFlt1 affect the health of the mother's small blood vessels, and ultimately lead to the telltale symptoms of preeclampsia.
"These findings provide us with an important piece of information as we work to develop strategies to treat preeclampsia," notes Karumanchi. "We're obviously a number of years away from being able to put these to use in humans but these results are an important step in the process." Furthermore, adds study coauthor Vikas Sukhatme, M.D., Ph.D., this study has important implications for the use of anti-angiogenic therapies in the treatment of cancer.
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Contact: Bonnie Prescott
bprescot@bidmc.harvard.edu
617-667-7306
Beth Israel Deaconess Medical Center
4-Mar-2003