β₂-adrenergic receptor autoantibodies alleviated myocardial damage induced by β₁-adrenergic receptor autoantibodies in heart failure

β₁-adrenergic receptor autoantibodies (β₁-AAs) and β₂-adrenergic receptor autoantibodies (β₂-AAs) are present in patients with heart failure (HF); however, their interrelationship with cardiac structure and function remains unknown. This study explored the effects of the imbalance between β₁-AAs and β₂-AAs on cardiac structure and its underlying mechanisms in HF.

Patients with left systolic HF who suffered from coronary heart disease (65.9%) or dilated cardiomyopathy (34.1%) were divided into New York Heart Association Classes I–II (n = 51) and Classes III–IV (n = 37) and compared with healthy volunteers as controls (n = 41). Total immunoglobulin G from HF patient serum comprising β₁-AAs and/or β₂-AAs were determined and purified for in vitro studies from neonatal rat cardiomyocytes (NRCMs). In addition, HF was induced by doxorubicin in mice. We observed that the increased ratio of β₁-AAs/β₂-AAs was associated with worsening HF in patients. Moreover, β₂-AAs from patients with HF suppressed the hyper-shrinking and apoptosis of NRCMS induced by β₁-AAs from some patients. Finally, β₂-AAs alleviated both myocardial damage and β₁-AAs production induced by doxorubicin in mice.

β₂-AAs were capable of antagonizing the effects imposed by β₁-AAs both in vitro and in vivo. The imbalance of β₁-AAs and β₂-AAs in patients with HF is a mechanism underlying HF progression, and the increasing ratio of β₁-AAs/β₂-AAs should be considered a clinical assessment factor for the deterioration of cardiac function in patients with HF.