Biological effects of the autoantibody against β₃-adrenoceptor from the sera of rats with heart failure     

LI Mei-xia  ZHANG Hai-feng  ZHANG Yan-qing  HE Zhong-mei  LIU Xiao-jun  ZHAO Rong-rui  LIU-Hui-rong 《园艺学报》2006,22(12):2340-2344

AIM:To investigate the relation between myocardial remodeling and the genesis of serum anti-β₃-adrenoceptor autoantibody, an animal model of heart failure (HF) was established and the biological effects of the autoantibody were observed.METHODS:(1) Healthy male Wistar rats were subjected to HF by constricting the abdominal aorta. (2) The anti-β₃-adrenoceptor autoantibody in the sera of HF rats was detected by ELISA with the synthetic peptide of the second extracellular loop of the β₃-adrenoceptor used as the antigen. (3) IgG in the positive sera from HF rats was prepared using a MabTrap Kit (Amersham). (4) The effects of the autoantibody on the contractile response of adult isolated cardiomyocytes and on the beating rate of cultured neonatal rat cardiomyocytes were observed.RESULTS:(1) The positive rate of anti-β₃-adrenoceptor autoantibody of rats increased from 21.05% of pretreatment to 78.95% after heart failure (P<0.01). The antibody mean titer of rats increased from 1∶19.49±1.41 of pretreatment to 1∶152.79±2.89 after heart failure (P<0.01). (2) The autoantibody against β₃AR from HF rats reduced systolic and diastolic responses in adult isolated cardiomyocytes, which was not modified by pretreating myocytes with nadolol (β₁AR and β₂AR antagonist), but was nearly prevented by bupranolol (nonselective β₁AR, β₂AR and β₃AR antagonist) or β₃AR specific antigen. (3) The autoantibody decreased the beating rate in cultured neonatal rat cardiomyocytes, which persisted within 6 hours and was also not modified by pretreating myocytes with nadolol, but was nearly prevented by bupranolol or β₃AR specific antigen. CONCLUSION:Our present study demonstrated that the higher titer of the autoantibody against β3AR generated by myocardial remodeling process during HF, which induced negative inotropic and chronotropic effects, may be a possibility of involvement in the pathophysiological mechanisms leading to heart failure.  相似文献