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Preeclampsia (PE) is a potentially life-threatening disorder during pregnancy, putting the mother and the new born at an increased risk for disease and death. PE is frequent, affecting 3-5% of pregnancies worldwide, making it the leading cause of maternal and fetal morbidity and mortality. The causes and mechanisms involved in the origin and progression of PE remain unresolved and medical therapies are accordingly lacking.
The delivery of placenta remains the only effective remedy resulting in pre-term delivery, which in itself constitutes an increased risk for the newborn. A group of researchers lead by the team of Prof. Berend Isermann, Otto-von-Guericke University, Magdeburg, now unraveled a key step in the manifestation of PE, which improves our understanding of PE. These results are expected to lead to new therapeutic approaches to defeat PE. The findings of this study has been recently published by the journal “Blood”.
PE has its origin within the placenta, but affects multiple organ systems causing hypertension (> 140/90 mmHg), renal dysfunction (proteinuria, glomerular endotheliosis), elevated liver enzymes, and a hypercoaguble vascular system. The events can be catastrophic, leading to a frequently lethal condition known as HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. Platelets are key regulators of blood coagulation system and enhanced platelet activation has been associated with PE. Also, women with PE have been shown to have higher count of extracellular vesicles (EV), cell-fragments shed from inflamed cells. The association of EV and platelet activation with PE is known, but how this may contribute to the disease and whether this can be therapeutically target remained unknown hitherto.
Berend Isermann, Shrey Kohli and colleagues identified in their work a new function of platelets and EVs in PE. Platelets and EVs cause a thrombo-inflammatory disorder at the feto-maternal interface. Procoagulant EVs activate platelets, which accumulate particularly within the placental vascular bed. There the platelets release ATP and thus cause inflammasome activation in the embryonic trophoblast. This leads to fetal death, intra-uterine growth restriction, renal failure, and maternal hypertension – all hallmarks of PE in humans. The investigators corroborated the relevance of these findings for human patients with PE in close cooperation with the gynecology departments at the university in Magdeburg and Erlangen and the local city hospital in Magdeburg. Importantly, anti-platelet agents such as Aspirin or pharmaceutics targeting the inflammasome pathway such as Anakinra, Apyrase or purinergic receptor antagonists inhibit the thrombo-inflammatory response within the placenta and prevent the manifestation of PE. Thus, these results, which were published in Blood, the leading journal for hemostasis and blood-cell related diseases, identify a new mechanism causing PE and suggest new therapeutic targets allowing to target PE.
Blood 2016 :blood-2016-03-705434; doi:10.1182/blood-2016-03-705434
http://www.bloodjournal.org/content/early/2016/09/02/blood-2016-03-705434.long?s...
Legend: Double immunofluorescence staining showing activated platelets (CD62P, P-selectin; red) in the placenta (left), but not in the kidney (right), after injections of mouse endothelial cell derived EV. CD62P (red) co-localizes (yellow) with GP1bα (green) indicating presence of activated platelets within the placenta (Placenta, upper left panel). Co-localization (yellow) of activated platelets (CD62P; red) and Gcm-1 positive syncytiotrophoblast (arrows, green) indicates direct contact of activated platelets with syncytiotrophoblasts, which line maternal blood spaces within the placenta; (Placenta, lower left panel); arrow heads: autofluorescence of erythrocytes.
Contact: Prof. Dr. Berend Isermann and Shrey Kohli
Shrey Kohli (AG Isermann)
Institute for Clinical Chemistry and Pathobiochemistry
Otto-von-Guericke Univeristy (Medical Faculty)
Leipziger Str. 44, 39120 Magdeburg
Germany
Tel.: +49 391 67-13921
E-Mail: berend.isermann@med.ovgu.de und shrey.kohli@med.ovgu.de
Activated platelets in the placenta after extracellular vesicle injections
Autor: Shrey Kohli
None
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Activated platelets in the placenta after extracellular vesicle injections
Autor: Shrey Kohli
None
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