Disturbance of myocardial metabolism participates in autoantibodies against β 1 ‐adrenoceptor‐induced cardiac dysfunction

Cardiac dysfunction is involved in disorders of energy metabolism. High‐titre autoantibodies against the β 1 ‐adrenoceptor (β 1 ‐AAs) have been reported to exist in patients with cardiac dysfunction; however, the mechanism by which β 1 ‐AAs affect cardiac function is unknown. This study aimed to determine whether β 1 ‐AAs disturb myocardium energy metabolism and cause cardiac dysfunction. β 1 ‐AA monoclonal antibodies (β 1 ‐AAmAbs) were successfully pre‐synthesized by hybridoma clones and used in all experiments. β 1 ‐AAmAbs impaired cardiac function and induced a myocardial metabolic disturbance, as evidenced by decreased left ventricular ejection fraction and fractional shortening. In addition, β 1 ‐AAmAbs decreased the adenosine triphosphate level and increased cardiac energy consumption (rate–pressure product). We further showed that the effects of β 1 ‐AAmAbs on heart tissue might involve the mitochondria and metabolic pathways via the β 1 ‐adrenoceptor based on an immunoprecipitation and mass spectrometry. Additionally, we found that β 1 ‐AAmAbs impaired myocardial mitochondrial structure, decreased the membrane potential, and induced insufficient mitophagy. In conclusion, β 1 ‐AAmAb‐induced cardiac dysfunction is partly due to a disturbance in myocardial energy metabolism.