The Mayo Clinic work is the first to link high levels of HtrA1 in third-trimester placental tissues with severe preeclampsia. The results will be reported at the Society for Maternal-Fetal Medicine annual meeting in Miami.
Though preliminary, the findings may one day lead to development of a blood test to track HtrA1 levels to identify women at risk of preeclampsia. Currently no predictive test exists for preeclampsia.
Notes Brian Brost, M.D., Mayo Clinic high-risk pregnancy specialist and senior study investigator, "It is certainly too early to say HtrA1 is a biomarker of preeclampsia, but the initial results are really encouraging, because the cause of this serious complication of pregnancy has not been well understood."
Funminiyi Ajayi, M.D., Mayo researcher and co-author of the paper, collected the placental samples and reviewed the results. "From a basic science point of view, this is an important contribution to understanding a complex series of events that we hope one day to be able to reverse or prevent," says Dr. Ajayi.
Significance of the Mayo Clinic Research
The Mayo Clinic researchers are the first to take two important steps toward developing a better understanding of preeclampsia. These "firsts" consist of:
Background Biology
Prior to the current Mayo Clinic investigation, the protein HtrA1 was known to be involved in programmed cell death, cell change and "invasiveness," the ability of cells to invade and colonize new areas. This process can be healthy -- as in establishing growth of a placenta in the uterus during the first trimester. Invasion also can be unhealthy -- as in the cases of cancer, another context in which the role of HtrA1 has been well studied.
In the Mayo Clinic investigation into HtrA1 and preeclampsia, findings suggest that the increased levels of HtrA1 impair correct functioning during the second stage of growth of key placental cells called cytotrophoblasts. Their job is to invade the uterus to establish the placenta. Just how HtrA1 does this is not known. One possibility is that its molecules "fit" into place in the molecular puzzle to activate abnormal growth. This is theoretically possible because HtrA1 molecules are structurally similar to other molecules, insulin-like growth factors (IGF) binding proteins, according to the Mayo Clinic researchers. Research has shown that an excess IGF binding protein disrupts the growth of cytotrophoblasts and also leads to the dysfunction of the placenta and impaired fetal growth.
Collaboration and Support
In addition to Drs. Brost and Ajayi, the Mayo Clinic research team included Jeremy Chien, Ph.D., Thomas Gaffey, M.D., and William Watson, M.D.