Antibodies From Preeclamptic Patients Stimulate Increased Intracellular Ca 2+ Mobilization Through Angiotensin Receptor Activation
| العنوان: | Antibodies From Preeclamptic Patients Stimulate Increased Intracellular Ca 2+ Mobilization Through Angiotensin Receptor Activation |
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| المؤلفون: | Mary Clare Day, Theingi M. Thway, Barbara M. Sanborn, Sergiy G. Shlykov, Rodney E. Kellems, Larry C. Gilstrap, Yang Xia |
| المصدر: | Circulation. 110:1612-1619 |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2004. |
| سنة النشر: | 2004 |
| مصطلحات موضوعية: | Adult, medicine.medical_specialty, Angiotensin receptor, Transcription, Genetic, Dose-Response Relationship, Immunologic, CHO Cells, Transfection, Autoantigens, Receptor, Angiotensin, Type 1, Preeclampsia, Epitopes, Pre-Eclampsia, Genes, Reporter, Pregnancy, Cricetinae, Physiology (medical), Internal medicine, medicine, Animals, Humans, Platelet, Calcium Signaling, Receptor, Autoantibodies, Luciferases, Renilla, Angiotensin II receptor type 1, NFATC Transcription Factors, business.industry, Nuclear Proteins, medicine.disease, Angiotensin II, Peptide Fragments, Rats, DNA-Binding Proteins, Endocrinology, Gene Expression Regulation, Immunoglobulin G, Female, Signal transduction, Cardiology and Cardiovascular Medicine, business, Intracellular, Transcription Factors |
| الوصف: | Background— Preeclampsia is a serious disorder of pregnancy characterized by hypertension, proteinuria, edema, and coagulation and vascular abnormalities. At the cellular level, abnormalities include increased calcium concentration in platelets, lymphocytes, and erythrocytes. Recent studies have shown that antibodies directed against angiotensin II type I (AT 1 ) receptors are also highly associated with preeclampsia. Methods and Results— We tested the hypothesis that AT 1 receptor–agonistic antibodies (AT 1 -AAs) could activate AT 1 receptors, leading to an increased intracellular concentration of free calcium and to downstream activation of Ca 2+ signaling pathways. Sera of 30 pregnant patients, 16 diagnosed with severe preeclampsia and 14 normotensive, were examined for the presence of IgG capable of stimulating intracellular Ca 2+ mobilization. IgG from all preeclamptic patients activated AT 1 receptors and increased intracellular free calcium. In contrast, none of the normotensive individuals had IgG capable of activating AT 1 receptors. The specific mobilization of intracellular Ca 2+ by AT 1 -AAs was blocked by losartan, an AT 1 receptor antagonist, and by a 7-amino-acid peptide that corresponds to a portion of the second extracellular loop of the AT 1 receptor. In addition, we have shown that AT 1 -AA–stimulated mobilization of intracellular Ca 2+ results in the activation of the transcription factor, nuclear factor of activated T cells. Conclusions— These results suggest that maternal antibodies capable of activating AT 1 receptors are likely to account for increased intracellular free Ca 2+ concentrations and changes in gene expression associated with preeclampsia. |
| تدمد: | 1524-4539 0009-7322 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3698d3e5af21b9049a49845672466b03Test https://doi.org/10.1161/01.cir.0000142855.68398.3aTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....3698d3e5af21b9049a49845672466b03 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15244539 00097322 |
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