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β3-adrenoceptors (β3-ARs) mediate a negative inotropic effect in human ventricular cardiomyocytes, which is opposite to that of β1- and β2-ARs. It has been previously demonstrated that autoantibodies against the β1/β2-AR exist in the sera of some patients with heart failure (HF) and these autoantibodies display agonist-like effects. Our aim in this study was to observe whether autoantibodies against the β3-AR (β3-AR Abs) exist in the sera of patients with HF and to assess the effects of β3-AR Abs on rat model of pressure overload cardiomyopthy. In the present study, the level of β3-AR Abs in the sera of HF patients was screened by ELISA. β3-AR Abs from HF patients were administrated to male adult rats with abdominal aortic banding (AAB), and the cardiac function was measured by echocardiographic examination and hemodynamic studies. The biological effects of this autoantibody on cardiomyocytes were evaluated using a motion-edge detection system, intracellular calcium transient assay, and patch clamp techniques. Compared to healthy subjects, the frequency of occurrence and titer of β3-AR Abs in the sera of HF patients were greatly increased, and β3-AR Abs could prevent LV dilation and improve the cardiac function of rats with AAB. β3-AR Abs exhibited negative chronotropic and inotropic effects and were accompanied by a decreased intracellular Ca2+ transient and membrane L-type Ca2+ current in cardiomyocytes. Our results demonstrated the existence of β3-AR Abs in the sera of patients with HF and found that this autoantibody could alleviate the cardiac dysfunction induced by pressure-overload in AAB rats. [ABSTRACT FROM AUTHOR]

Abstract: Background: β1-Adrenoceptors (β1-ARs) are the predominant receptors in regulating heart functions. β1-ARs contain 7-transmembrane domains (7TM), 3 extracellular loops and 3 intracellular loops. Among these loops, the second extracellular loop of β1-AR (β1-AR-ECII) plays an important role in the pathogenesis of heart failure. Methods: (1) Select the sera-negative rats for antibodies against β1-AR-ECII. (2) Detect the level of antibodies against β1-AR-ECII in the process of active immunization with artificial synthetic peptides according to the sequence of human β1-AR-ECII. (3) Observe its long-term role on cardiac structure and function in vivo by immunizing rats. (4) Detect the changes of T lymphocytes subsets in the process of active immunization. Results: The peptides induced the production of specific autoantibody against β1-AR-ECII. Furthermore, immunization with β1-AR-ECII peptide induced both morphological and functional alterations in the hearts of rats, which potentially results in heart failure. In addition, induction of the autoantibodies against β1-AR-ECII increased the CD4 +/CD8 + ratio in the peripheral blood of rats. Discussion: In this study, we determined the effect of anti-β1-AR-ECII autoantibody on morphological and functional cardiomyopathic alterations by immunization of rats with a synthetic peptide corresponding to the β1-AR-ECII for 18months. These results provide further evidence that autoantibody against β1-AR-ECII is involved in the pathogenesis of heart failure. But the underlying mechanisms need further study. [Copyright &y& Elsevier]