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.
(© 2021 John Wiley & Sons Australia, Ltd.)