Disturbance of myocardial metabolism participates in autoantibodies against β1 -adrenoceptor-induced cardiac dysfunction.

Cardiac dysfunction is involved in disorders of energy metabolism. High-titre autoantibodies against the β1 -adrenoceptor (β1 -AAs) have been reported to exist in patients with cardiac dysfunction; however, the mechanism by which β1 -AAs affect cardiac function is unknown. This study aimed to determine whether β1 -AAs disturb myocardium energy metabolism and cause cardiac dysfunction. β1 -AA monoclonal antibodies (β1 -AAmAbs) were successfully pre-synthesized by hybridoma clones and used in all experiments. β1 -AAmAbs impaired cardiac function and induced a myocardial metabolic disturbance, as evidenced by decreased left ventricular ejection fraction and fractional shortening. In addition, β1 -AAmAbs decreased the adenosine triphosphate level and increased cardiac energy consumption (rate-pressure product). We further showed that the effects of β1 -AAmAbs on heart tissue might involve the mitochondria and metabolic pathways via the β1 -adrenoceptor based on an immunoprecipitation and mass spectrometry. Additionally, we found that β1 -AAmAbs impaired myocardial mitochondrial structure, decreased the membrane potential, and induced insufficient mitophagy. In conclusion, β1 -AAmAb-induced cardiac dysfunction is partly due to a disturbance in myocardial energy metabolism.