Pro-apoptotic and Cardiodepressive Effect of the Anti-β1- Adrenoceptor Antibody in Rat.

Objective: To investigate whether immunization with synthetic peptides corresponding to the second extracellular loop of the β₁-adrenoceptor (β₁-AR-EC_u) may induce myocardial apoptosis in vivo, and if so, to determine whether apoptosis may contribute to cardiac dysfunction. Methods and Results: Adult male Wistar rats were immunized with synthetic peptides for 9 weeks. Anti-β₁-AR antibody, cardiomyocyte apoptosis and cardiac function were determined. In the vehicle group, the antibody titer remained below 1:10 and no myocardial apoptosis and cardiac functional change were observed. However, in the immunized rats, a significant increase in anti-β₁-AR antibody occurred 2 weeks after the immunization and peaked at week 3. A significant increase in caspase 3 occurred at week 3 and peaked at week 4, and severe cardiac dysfunction occurred 7 weeks. Treatment with Z-VAD-FMK, a broad-spectrum caspase inhibitor abolished myocardial apoptosis and improved cardiac function in the immunization rats. Conclusion: Our results demonstrated that stimulation with the antibody against β₁-AR-EC_u induces cardiomyocyte apoptosis in vivo contributing to cardiac dysfunction, and suggest that anti-apoptotic treatments may be a novel strategy in reducing multiple organ injury associated with immune response. [ABSTRACT FROM AUTHOR]