Abstract 17544: Beta1-Adrenergic Receptor Autoantibodies from Heart Failure Rats Enhanced the Proliferation of T Lymphocytes Largely in PKA-Dependent Fashion
Background: Autoantibody against the second extracellular loop of beta1-adrengic receptor (beta1-AA) not only contributes to the increased susceptibility to heart failure, but also plays a causative role in myocardial remodeling by its sympathomimetic-like effects via binding with the beta1-adrengic receptor. Our previous studies have observed that long-term presence of beta1-AA lead to the myocardial damage with increased ratios of CD4+/CD8+ T lymphocytes. However, whether the beta1-AA could recognize the corresponding receptor, and therefore, interfere with T lymphocytes remains unclear. Using an in vitro simulated T lymphocytes activation model, we attempted to explore the role of beta1-AA from an animal model of post-MI heart failure in the proliferation of T lymphocytes.
Methods: Myocardial infarction was induced in adult male Wistar rats by ligating the left anterior descending coronary artery. Beta1-AA was acquired from sera of rats with heart failure. The CD3+T lymphocytes were selected separately through flow cytometry. The expression of beta1-adrengic receptor on the CD3+T lymphocytes was detected by confocal microscope, and the proliferation of the CD3+ T lymphocytes was examined by CCK-8 kits.
Results: Our results showed that beta1-adrengic receptor is expressed on the surface of CD3+T lymphocytes of rats. Meanwhile, beta1-AA from heart failure rats could promote the proliferation of CD3+T lymphocytes in vitro in a dose-dependent manner (0.115±0.003vs.0.0895±0.005, P<0.05; 0.117±0.001 vs. 0.0901±0.006, P<0.05; 0.128±0.03 vs.0.0925±0.0007, P<0.05), which could be fully blocked by selective beta1-adrengic receptor antagonist metoprolol (0.11±0.0075 vs. 0.0925 ±0.0007, P>0.05) and the PKA inhibitor H89 (0.098±0.05 vs. 0.0925±0.0007, P>0.05). Furthermore, beta1-AA induced an increase of the cyclic adenosine monophosphate (265±7.5pmol/mL vs. 109±5.8pmol/mL, P<0.01) in the CD3+T lymphocytes.
Conclusion: Our present study demonstrated for the first time that beta1-AA from heart failure rat could enhance the proliferation of CD3+T lymphocytes, which may contribute to a more comprehensive understanding of the immune effects of beta1-AA on heart failure.
- © 2011 by American Heart Association, Inc.