The application of dynamic models to the exploration of \(\beta_1\)-AR overactivation as a cause of heart failure (Q1632595)

Summary: High titer of \(\beta_1\)-adrenoreceptor autoantibodies (\(\beta_1\)-AA) has been reported to appear in heart failure patients. It induces sustained \(\beta_1\)-adrenergic receptor (\(\beta_1\)-AR) activation which leads to heart failure (HF), but the mechanism is as yet unclear. In order to investigate the mechanisms causing \(\beta_1\)-AR non-desensitization, we studied the beating frequency of the neonatal rat cardiomyocytes (NRCMs) under different conditions (an injection of isoprenaline (ISO) for one group and \(\beta_1\)-AA for the other) and established three dynamic models in order to best describe the true relationships shown in medical experiments; one model used a control group of healthy rats; then in HF rats one focused on conformation changes in \(\beta_1\)-AR; the other examined interaction between \(\beta_1\)-AR and \(\beta_2\)-adrenergic receptors (\(\beta_2\)-AR). Comparing the experimental data and corresponding Akaike information criterion (AIC) values, we concluded that the interaction model was the most likely mechanism. We used mathematical methods to explore the mechanism for the development of heart failure and to find potential targets for prevention and treatment. The aim of the paper was to provide a strong theoretical basis for the clinical development of personalized treatment programs. We also carried out sensitivity analysis of the initial concentration \(\beta_1\)-AA and found that they had a noticeable effect on the fitting results.