ArticleHypertension (Dallas, Tex. : 1979)2011
Angiotensin II type 1 receptor antibodies and increased angiotensin II sensitivity in pregnant rats.
Article in Hypertension (Dallas, Tex. : 1979), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 132 citations in OpenAlex.
- Increased ATCell death & disease · 2020Trial
- Sex differences in the developmental programming of cardiovascular and renal risk across the lifespan.American journal of physiology. Renal physiology · 2026Review
- Article
- Role of agonistic autoantibodies to the angiotensin II type 1 receptor (AT1-AA) in pathogenesis of preeclampsia.Global medical genetics · 2025Review
- Maternal Microvascular Dysfunction During and After Preeclamptic Pregnancy.Comprehensive Physiology · 2024Review
- Association of Angiotensin II Receptor Type 1 and Endothelin-1 Receptor Type A Agonistic Autoantibodies With Adverse Remodeling and Cardiovascular Events After Acute Myocardial Infarction.Journal of the American Heart Association · 2024Observational
- AT1-AA Is Produced in Offspring in Response to Placental Ischemia and Is Lowered by B-Cell Depletion Without Compromising Overall Offspring Health.Journal of the American Heart Association · 2024Article
- Autoimmune Implications in a Patient with Graves' Hyperthyroidism, Pre-eclampsia with Severe Features, and Primary Aldosteronism.Medicina (Kaunas, Lithuania) · 2024Article
- Association between Serum 8-Iso-Prostaglandin F2α as an Oxidative Stress Marker and Immunological Markers in a Cohort of Preeclampsia Patients.Life (Basel, Switzerland) · 2023Article
- Advances in the allostery of angiotensin II type 1 receptor.Cell & bioscience · 2023Review
- A novel vaccine targeting β1-adrenergic receptor.Hypertension research : official journal of the Japanese Society of Hypertension · 2023Article
- The role of immune cells and mediators in preeclampsia.Nature reviews. Nephrology · 2023Review
- Animal Models of Cardiovascular Complications of Pregnancy.Circulation research · 2022Review
- Novel allosteric ligands of the angiotensin receptor AT1R as autoantibody blockers.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Considerations to Model Heart Disease in Women with Preeclampsia and Cardiovascular Disease.Cells · 2021Review
- Autoantibodies as Endogenous Modulators of GPCR Signaling.Trends in pharmacological sciences · 2021Review
- Article
- Angiotensin II Type 1 Receptor Autoantibodies in Primary Aldosteronism.Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme · 2020Review
- RNA interference therapeutics targeting angiotensinogen ameliorate preeclamptic phenotype in rodent models.The Journal of clinical investigation · 2020Article
- From animal models to patients: the role of placental microRNAs, miR-210, miR-126, and miR-148a/152 in preeclampsia.Clinical science (London, England : 1979) · 2020Review
10 more citing papers are in PubMed but not listed here.
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Authors and funding
21 authors at 6 institutions in 3 countries.
Funding
Abstract
Pregnant women who subsequently develop preeclampsia are highly sensitive to infused angiotensin (Ang) II; the sensitivity persists postpartum. Activating autoantibodies against the Ang II type 1 (AT(1)) receptor are present in preeclampsia. In vitro and in vivo data suggest that they could be involved in the disease process. We generated and purified activating antibodies against the AT(1) receptor (AT(1)-AB) by immunizing rabbits against the AFHYESQ epitope of the second extracellular loop, which is the binding epitope of endogenous activating autoantibodies against AT(1) from patients with preeclampsia. We then purified AT(1)-AB using affinity chromatography with the AFHYESQ peptide. We were able to detect AT(1)-AB both by ELISA and a functional bioassay. We then passively transferred AT(1)-AB into pregnant rats, alone or combined with Ang II. AT(1)-AB activated protein kinase C-α and extracellular-related kinase 1/2. Passive transfer of AT(1)-AB alone or Ang II (435 ng/kg per minute) infused alone did not induce a preeclampsia-like syndrome in pregnant rats. However, the combination (AT(1)-AB plus Ang II) induced hypertension, proteinuria, intrauterine growth retardation, and arteriolosclerosis in the uteroplacental unit. We next performed gene-array profiling of the uteroplacental unit and found that hypoxia-inducible factor 1α was upregulated by Ang II plus AT(1)-AB, which we then confirmed by Western blotting in villous explants. Furthermore, endothelin 1 was upregulated in endothelial cells by Ang II plus AT(1)-AB. We show that AT(1)-AB induces Ang II sensitivity. Our mechanistic study supports the existence of an "autoimmune-activating receptor" that could contribute to Ang II sensitivity and possible to preeclampsia.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.