Sera from Preeclampsia Patients Elicit Symptoms of Human Disease in Mice and Provide a Basis for an in Vitro Predictive Assay
| Autor: | Leif Matthiesen, Wendy E. Norris, Surendra Sharma, R. Boij, James F. Padbury, Jonathan D. Kurtis, Kee-Hak Lim, Satyan Kalkunte, Jennifer F. Friedman, Zhongbin Lai |
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| Rok vydání: | 2010 |
| Předmět: |
Serum
medicine.medical_specialty Blood Pressure Gestational Age Disease Kidney Pathology and Forensic Medicine Preeclampsia Mice Pre-Eclampsia Pregnancy medicine Animals Humans Hypoxia reproductive and urinary physiology Mice Knockout Fetus Vascular Endothelial Growth Factor Receptor-1 business.industry Anatomical pathology Hypoxia (medical) medicine.disease female genital diseases and pregnancy complications Interleukin-10 Disease Models Animal Interleukin 10 embryonic structures Immunology Gestation Biological Assay Female medicine.symptom business Regular Articles |
| Zdroj: | The American Journal of Pathology. 177:2387-2398 |
| ISSN: | 0002-9440 |
| DOI: | 10.2353/ajpath.2010.100475 |
| Popis: | Early diagnosis and treatment of preeclampsia would significantly reduce maternal and fetal morbidity and mortality. However, its etiology and prediction have remained elusive. Based on the hypothesis that sera from patients with preeclampsia could function as a “blueprint” of causative factors, we describe a serum-based pregnancy-specific mouse model that closely mirrors the human condition as well as an in vitro predictive assay. We show that a single administration of human preeclampsia serum in pregnant IL-10−/− mice induced the full spectrum of preeclampsia-like symptoms, caused hypoxic injury in uteroplacental tissues, and elevated soluble fms-like tyrosine kinase 1 and soluble endoglin, markers thought to be related to the disease. The same serum sample(s) induced a partial preeclampsia phenotype in wild-type mice. Importantly, preeclampsia serum disrupted cross talk between trophoblasts and endothelial cells in an in vitro model of endovascular activity. Disruption of endovascular activity could be documented in serum samples as early as 12 to 14 weeks of gestation from patients who subsequently developed preeclampsia. These results indicate that preeclampsia patient sera can be used to understand the pregnancy-specific disease pathology in mice and can predict the disorder. |
| Databáze: | OpenAIRE |
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