Identification of a Novel Agonist-Like Autoantibody in Preeclamptic Patients
| العنوان: | Identification of a Novel Agonist-Like Autoantibody in Preeclamptic Patients |
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| المؤلفون: | Elizabeth Portugal Pimenta Velloso, Gerd Wallukat, Renata Lúcia Pimentel, Robson A.S. Santos, Antônio Carlos Vieira Cabral, Zilma Silveira Nogueira Reis, Janaina F Braga, Michael Bader |
| المصدر: | American Journal of Hypertension. :hpv099 |
| بيانات النشر: | Oxford University Press (OUP), 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Adult, Endothelin Receptor Antagonists, Agonist, medicine.medical_specialty, medicine.drug_class, Pregnancy Trimester, Third, Tetrazoles, Gestational Age, Naphthalenes, Peptides, Cyclic, Severity of Illness Index, Receptor, Angiotensin, Type 1, Young Adult, chemistry.chemical_compound, Pre-Eclampsia, Heart Rate, Pregnancy, Internal medicine, Internal Medicine, Animals, Humans, Medicine, Myocytes, Cardiac, Enzyme Inhibitors, Rats, Wistar, Receptor, Protein Kinase C, Autoantibodies, Angiotensin II receptor type 1, business.industry, Biphenyl Compounds, Autoantibody, Irbesartan, Receptor, Endothelin A, Angiotensin II, Rats, Biphenyl compound, Endocrinology, Calphostin C, chemistry, Case-Control Studies, Female, business, Endothelin receptor, Angiotensin II Type 1 Receptor Blockers |
| الوصف: | BACKGROUND: Recent studies have shown that preeclampsia (PE) is associated with the presence of autoantibodies (AABs) that activate the angiotensin II AT1 receptor, which could contribute to many of the symptoms of PE. METHODS: To investigate the frequency and the targets of AABs in preeclamptic women (31 cases) and healthy pregnant normotensive women (29 cases) in Brazil, antibodies from serum samples were detected by a bioassay using spontaneously beating neonatal rat cardiomyocytes in culture. In the cardiomyocytes, the agonistic AABs induce a positive or negative chronotropic response, mimicking the corresponding receptor agonists. The specificity of the AAB response was identified by specific receptor antagonists. RESULTS: Thirty preeclamptic patients (97%) presented AABs against the angiotensin II AT1 receptor. The agonistic effect of the AAB was blocked by irbesartan and neutralized by a peptide corresponding to the second extracellular loop of this receptor. Strikingly, we discovered that all sera from the severe preeclamptic patients (16 cases) contained a novel agonist-like AAB directed against the endothelin-1 ETA receptor in addition to the AABs against the angiotensin II AT1 receptor. This AAB was selectively blocked by the antagonist BQ-123, antagonized by the protein kinase C (PKC) inhibitor Calphostin C and neutralized by peptides corresponding to the second extracellular loop of the endothelin-1 ETA receptor subtype. CONCLUSIONS: We described, for the first time, the presence of endothelin-1 ETA receptor AABs in PE. Our results suggest that the presence of both agonistic AABs may be involved in the pathogenesis of severe PE. |
| تدمد: | 1941-7225 0895-7061 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0cf9807bb69786b0135821c2dc535bc0Test https://doi.org/10.1093/ajh/hpv099Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....0cf9807bb69786b0135821c2dc535bc0 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19417225 08957061 |
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