1. Long-term active immunization with a synthetic peptide corresponding to the second extracellular loop of β1-adrenoceptor induces both morphological and functional cardiomyopathic changes in rats
- Author
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Zuo, Lin, Bao, Haijun, Tian, Jue, Wang, Xiaoliang, Zhang, Suli, He, Zhongmei, Yan, Li, Zhao, Rongrui, Ma, Xin L., and Liu, Huirong
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CARDIOMYOPATHIES , *IMMUNIZATION , *PEPTIDE synthesis , *BETA adrenoceptors , *HEART failure , *ANIMAL morphology , *LABORATORY rats , *HEART function tests , *AUTOANTIBODIES - Abstract
Abstract: Background: β1-Adrenoceptors (β1-ARs) are the predominant receptors in regulating heart functions. β1-ARs contain 7-transmembrane domains (7TM), 3 extracellular loops and 3 intracellular loops. Among these loops, the second extracellular loop of β1-AR (β1-AR-ECII) plays an important role in the pathogenesis of heart failure. Methods: (1) Select the sera-negative rats for antibodies against β1-AR-ECII. (2) Detect the level of antibodies against β1-AR-ECII in the process of active immunization with artificial synthetic peptides according to the sequence of human β1-AR-ECII. (3) Observe its long-term role on cardiac structure and function in vivo by immunizing rats. (4) Detect the changes of T lymphocytes subsets in the process of active immunization. Results: The peptides induced the production of specific autoantibody against β1-AR-ECII. Furthermore, immunization with β1-AR-ECII peptide induced both morphological and functional alterations in the hearts of rats, which potentially results in heart failure. In addition, induction of the autoantibodies against β1-AR-ECII increased the CD4 +/CD8 + ratio in the peripheral blood of rats. Discussion: In this study, we determined the effect of anti-β1-AR-ECII autoantibody on morphological and functional cardiomyopathic alterations by immunization of rats with a synthetic peptide corresponding to the β1-AR-ECII for 18months. These results provide further evidence that autoantibody against β1-AR-ECII is involved in the pathogenesis of heart failure. But the underlying mechanisms need further study. [Copyright &y& Elsevier]
- Published
- 2011
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