Pro-remodeling effect of autoantibody against β1-adrenoceptor on cardiomyocytes involves T cells dysfunction under the pathological condition of heart failure.

Abstract

Autoantibody against β1-adrenoceptor (β1-AA) has been shown to be closely linked to the aggravation of heart failure. Removal of β1-AA remarkably attenuated patients' cardiac dysfunction. We found that β1-AA induced rat heart failure with increased CD4+ T cells. However, whether or not β1-AA interacts with T cells isolated from heart failure patients remains unknown. Twenty-one β1-AA-negative heart failure patients were divided into those taking β-adrenergic blocker and those not. The effects of β1-AA monoclonal antibodies (β1-AAmAb) on T cells proliferation were detected using the CCK-8 assay. IFN-γ and IL-4 production by human T cells were measured by after the administration of β1-AAmAb. The levels of cardiomyocyte apoptosis and hypertrophy were detected after co-cultured with the supernatant of T cells pre-stimulated by β1-AAmAb. It was found that β1-AAmAb promoted T cell proliferation via the β1-AR/cAMP/PKA pathway in patients who not take β-blocker. β1-AAmAb inhibited the characteristic cytokine secretion of Th1, IFN-γ, but had no significant effect on the Th2 cytokine IL-4. Supernatant resulted from the T cells pre-treated with β1-AAmAb induced cardiomyocytes remodeling, as evidenced by increased levels of cardiomyocytes apoptosis and hypertrophy. We propose that heart failure is likely to be an interference factor for Th-mediated immunity, and the presence of β1-AAmAb may aggravate this effect and deteriorate concomitant inflammatory injury in cardiomyocytes, partially via β1-AR/cAMP/PKA pathway.

• Authors: Yunhui Du, Shihan Zhang, Wenjing Hao, Wenli Xu, Li Yan, Huirong Liu
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 510 Issue 1 Pg. 163-170 (02 26 2019) ISSN: 1090-2104 [Electronic] United States
• PMID: 30678811 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Adrenergic beta-1 Receptor Antagonists
• Autoantibodies
• Receptors, Adrenergic, beta-1
• Cyclic AMP
• Cyclic AMP-Dependent Protein Kinases

Topics

• Adrenergic beta-1 Receptor Antagonists (administration & dosage, therapeutic use)
• Autoantibodies (pharmacology)
• Cell Proliferation (drug effects)
• Coculture Techniques
• Cyclic AMP (metabolism)
• Cyclic AMP-Dependent Protein Kinases (metabolism)
• Heart Failure (immunology, pathology)
• Humans
• Myocytes, Cardiac (drug effects)
• Receptors, Adrenergic, beta-1 (immunology)
• T-Lymphocytes (pathology)
• T-Lymphocytes, Helper-Inducer (immunology)