Disturbance of myocardial metabolism participates in autoantibodies against beta(1)-adrenoceptor-induced cardiac dysfunction

摘要

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