Perfusion of human placenta with hemoglobin introduces preeclampsia-like injuries that are prevented by α1-microglobulin
| Autor: | Sigurbjörg Rutardottir, Magnus Centlow, Werner Siegmund, Bo Åkerström, Martin Cederlund, Mattias Olsson, Irene Larsson, K May, Lena Wester Rosenlöf, Henning Schneider, Stefan R. Hansson, Matthias Mörgelin |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities medicine.medical_specialty Placenta In Vitro Techniques Microarray Biology medicine.disease_cause Preeclampsia Hemoglobins Pre-Eclampsia Pregnancy Obstetrics Gynecology and Reproductive Medicine hemic and lymphatic diseases Internal medicine Alpha-Globulins Fetal hemoglobin Electron microscopy medicine Humans Hemoglobin Fetal Hemoglobin Oxygenated Hemoglobin Beta-2 microglobulin Gene Expression Profiling Dual placental perfusion Obstetrics and Gynecology medicine.disease Up-Regulation Perfusion Oxidative Stress medicine.anatomical_structure Endocrinology Reproductive Medicine Oxidative stress alpha(1)-microglobulin Female Alpha-1-microglobulin Developmental Biology |
| Zdroj: | Placenta; 32(4), pp 323-332 (2011) |
| ISSN: | 0143-4004 1532-3102 |
| DOI: | 10.1016/j.placenta.2011.01.017 |
| Popis: | Preeclamptic women have increased plasma levels of free fetal hemoglobin (HbF), increased gene expression of placental HbF and accumulation of free HbF in the placental vascular lumen. Free hemoglobin (Hb) is pro-inflammatory, and causes oxidative stress and tissue damage.To show the impact of free Hb in PE, we used the dual ex vivo placental perfusion model. Placentas were perfused with Hb and investigated for physical parameters, Hb leakage, gene expression and morphology. The protective effects of α(1)-microglobulin (A1M), a heme- and radical-scavenger and antioxidant, was investigated.Hb-addition into the fetal circulation led to a significant increase of the perfusion pressure and the feto-maternal leakage of free Hb. Morphological damages similar to the PE placentas were observed. Gene array showed up-regulation of genes related to immune response, apoptosis, and oxidative stress. Simultaneous addition of A1M to the maternal circulation inhibited the Hb leakage, morphological damage and gene up-regulation. Furthermore, perfusion with Hb and A1M induced a significant up-regulation of extracellular matrix genes.The ex vivo Hb-perfusion of human placenta resulted in physiological and morphological changes and a gene expression profile similar to what is observed in PE placentas. These results underline the potentially important role of free Hb in PE etiology. The damaging effects were counteracted by A1M, suggesting a role of this protein as a new potential PE therapeutic agent. |
| Databáze: | OpenAIRE |
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