Generation and biological effects of autoantibody against β1-adrenoceptor in the sera from rats with heart failure |
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| Authors: | HE Zhong-mei WANG Xiao-liang WANG Cai-ping YAN Zi WU Ye ZHAO Rong-rui LIU Hui-rong |
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| Institution: | 1.Department of Physiology, Shanxi Medical University;2.The First Hospital of Shanxi Medical University, Taiyuan 030001, China, E-mail:liuhr2000@126.com |
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| Abstract: | AIM:The present study was designed to examine the relationship between development of heart failure (HF) and the genesis of autoantibody against β1-adrenoceptor (β1AR) by establishing an adult rat model of HF, and explore the biological effects of the autoantibody and the signal pathway by which the anti-β1AR-autoantibody may contribute to the pathogenesis of HF. METHODS:Male adult rats were subjected to establish HF model by constricting the abdominal aorta. The autoantibody against β1AR from the sera of rats with HF was screened by ELISA assay. IgG in the positive sera of rats with HF was prepared by using a MabTrap Kit (Amersham) following the manufacturer’s instructions. The effects of β1AR autoantibody on the beating rate of cultured neonatal rat cardiomyocytes and on the activity of adenylate cyclase (AC) in adult isolated cardiomyocytes were observed. RESULTS:(1) The positive rate and the titer of anti-β1AR autoantibody in the sera of rats with HF ［82.8%, 1∶(67.3±2.4)］ were obviously higher than those in sham group ［5%, 1∶(17.3±2.0)］ (P<0.01). (2) The IgG in the positive sera from the rats with HF increased the beating rate of cultured neonatal rat cardiomyocytes, and enhanced the activity of AC in adult isolated cardiomyocytes, as evidenced by the increased cyclic adenosine monophosphate (cAMP) content. CONCLUSION:Taken together, these results demonstrated that HF induced the generation of autoantibody against β1AR in an animal model and the autoantibody possessed an ‘agonistic-like’ positive chronotropic effect, enhanced the activity of AC, suggesting that the autoantibody against β1AR may contribute to the pathogenesis of HF as an agonist through β1AR-Gs-AC-cAMP-PKA signal pathway. |
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