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Autoantibodies against the angiotensin receptor (AT1) in patients with hypertension
1Wallenberg Laboratory, Sahlgren's Hospital, University of Göteborg, Sweden.
Insights
Autoantibodies against the angiotensin II receptor (AT1) were found in patients with malignant hypertension, suggesting a role in the disease's development. These autoantibodies target a functional part of the AT1 receptor.
Area of Science:
- Cardiovascular Research
- Immunology
- Hypertension Pathophysiology
Background:
- Malignant hypertension is a severe form of hypertension with high mortality.
- The role of autoantibodies in the pathogenesis of hypertension is not fully understood.
- G-protein-coupled receptors are crucial in cardiovascular regulation.
Purpose of the Study:
- To investigate the presence of autoantibodies against cardiovascular G-protein-coupled receptors in patients with malignant hypertension.
- To determine if autoantibodies against angiotensin II receptor (AT1), bradykinin (B2), or angiotensin II subtype 2 (AT2) receptors are associated with malignant hypertension.
- To assess the functional activity of identified autoantibodies.
Main Methods:
- Sera from patients with malignant essential hypertension, malignant secondary hypertension, renovascular diseases, and healthy controls were analyzed.
- Enzyme immunoassay was used to detect autoantibodies against AT1, B2, and AT2 receptors.
- Sensitivity of the assay was determined.
- Affinity-purified autoantibodies were used to localize AT receptors and assess their effect on cardiomyocytes.
Main Results:
- Autoantibodies against the AT1 receptor were detected in 14% of patients with malignant essential hypertension and 33% with malignant secondary hypertension.
- No antibodies against B2 or AT2 receptors were found in any patient group.
- Purified autoantibodies from positive patients localized AT receptors and induced a positive chronotropic effect on neonatal rat cardiomyocytes.
Conclusions:
- Autoantibodies against a functional extracellular domain of human AT1 receptors exist in patients with malignant hypertension.
- These autoantibodies may play a role in the pathogenesis of malignant hypertension.
- Further research is warranted to elucidate the precise mechanisms involved.
Abstract:
Sera from patients with malignant essential hypertension (n = 14), malignant secondary hypertension mainly attributable to renovascular diseases (n = 12) and renovascular diseases without malignant hypertension (n = 11) and from normotensive healthy blood donors (n = 35) were studied for the presence of autoantibodies against G-protein-coupled cardiovascular receptors. Autoantibodies against the angiotensin II receptor (AT1) were detected in 14, 33, 18 and 14% of patients with malignant essential hypertension, malignant secondary hypertension, renovascular diseases and control patients, respectively. Sensitivity of the enzyme immunoassay was assessed as 5 microg/ml IgG. Patients did not show antibodies against bradykinin (B2) or angiotensin II subtype 2 (AT2) receptors. Autoantibodies affinity-purified from positive patients localized AT receptors in Chinese hamster ovary transfected cells, and displayed a positive chronotropic effect on cultured neonatal rat cardiomyocytes. These results demonstrate the existence of autoantibodies against a functional extracellular domain of human AT1 receptors in patients with malignant hypertension, and suggest that these autoantibodies might be involved in the pathogenesis of malignant hypertension.