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  • Title: 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: Zuo L, Bao H, Tian J, Wang X, Zhang S, He Z, Yan L, Zhao R, Ma XL, Liu H.
    Journal: Int J Cardiol; 2011 May 19; 149(1):89-94. PubMed ID: 20096470.
    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 18 months. 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.
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