Long-term active immunization with a synthetic peptide corresponding to the second extracellular loop of β 1-adrenoceptor induces both morphological and functional cardiomyopathic changes in rats

Abstract

Background β 1-Adrenoceptors (β 1-ARs) are the predominant receptors in regulating heart functions. β 1-ARs contain 7-transmembrane domains (7TM), 3 extracellular loops and 3 intracellular loops. Among these loops, the second extracellular loop of β 1-AR (β 1-AR-EC II) plays an important role in the pathogenesis of heart failure. Methods (1) Select the sera-negative rats for antibodies against β 1-AR-EC II. (2) Detect the level of antibodies against β 1-AR-EC II in the process of active immunization with artificial synthetic peptides according to the sequence of human β 1-AR-EC II. (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 β 1-AR-EC II. Furthermore, immunization with β 1-AR-EC II 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 β 1-AR-EC II increased the CD 4 +/CD 8 + ratio in the peripheral blood of rats. Discussion In this study, we determined the effect of anti-β 1-AR-EC II autoantibody on morphological and functional cardiomyopathic alterations by immunization of rats with a synthetic peptide corresponding to the β 1-AR-EC II for 18 months. These results provide further evidence that autoantibody against β 1-AR-EC II is involved in the pathogenesis of heart failure. But the underlying mechanisms need further study.