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Hemopexin activity and extracellular ATP in the pathogenesis of preeclampsia

PhD ceremony:Ms F. (Floor) Spaans
When:October 08, 2014
Supervisor:prof. dr. H. (Harry) van Goor
Co-supervisors:dr. M.M. (Marijke) Faas, Prof. W.W. Bakker
Where:Academy building RUG
Faculty:Medical Sciences / UMCG
Hemopexin activity and extracellular ATP in the pathogenesis of

Preeclampsia is the most prevalent pregnancy complication and is characterized by high blood pressure and proteins in the urine. Apart from delivery of the child, no treatment for preeclampsia is currently available. The exact cause if the disease is unknown, but it is thought that the placenta does not function well and secretes aberrant substances into the mother’s bloodstream. These substances can induce inflammation and damage blood vessels, which leads to the preeclamptic symptoms. One of these substances is ATP. In this thesis we studied how ATP can contribute to the symptoms of preeclampsia by infusing ATP into pregnant rats. We found that ATP stimulates inflammation during pregnancy, which induces placental damage and loss of essential proteins in the urine. We also found that ATP inhibits the activity of the acute phase protein hemopexin (Hx). During normal pregnancy, when no ATP is present, the Hx activity increases. This is important because it helps to prevent development of high blood pressure during pregnancy. In preeclampsia, due to increased ATP, the Hx activity is decreased. This could explain the high blood pressure in these women. To further study the role of ATP in preeclampsia, we tested whether breakdown of ATP, by alkaline phosphatase, inhibited the symptoms of preeclampsia after ATP infusion in the pregnant rat. This treatment partly inhibited the preeclamptic symptoms. Our findings about the role of ATP, inflammation, and Hx activity increased our knowledge about the disease process of preeclampsia and may be used to develop novel treatments.