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Pro‐apoptotic and Cardiodepressive Effect of the Anti‐β 1 ‐Adrenoceptor Antibody in Rat
Author(s) -
Wang XiaoLiang,
Li MeiXia,
Tian Jue,
Yang XiaoLi,
Jia Jia,
Ma XinLiang,
Liu HuiRong
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1343-d
Subject(s) - apoptosis , cardiac function curve , in vivo , antibody , medicine , immune system , immunization , antibody titer , caspase 3 , pharmacology , endocrinology , titer , immunology , biology , programmed cell death , heart failure , biochemistry , microbiology and biotechnology
Objective: To investigate whether immunization with synthetic peptides corresponding to the second extracellular loop of the β 1 ‐adrenoceptor (β 1 ‐AR‐EC II ) may induce myocardial apoptosis in vivo, and if so, to determine whether apoptosis may contribute to cardiac dysfunction. Methods and Results: Adult male Wistar rats were immunized with synthetic peptides for 9 weeks. Anti‐β 1 ‐AR antibody, cardiomyocyte apoptosis and cardiac function were determined. In the vehicle group, the antibody titer remained below 1:10 and no myocardial apoptosis and cardiac functional change were observed. However, in the immunized rats, a significant increase in anti‐β 1 ‐AR antibody occurred 2 weeks after the immunization and peaked at week 3. A significant increase in caspase 3 occurred at week 3 and peaked at week 4, and severe cardiac dysfunction occurred 7 weeks. Treatment with Z‐VAD‐FMK, a broad‐spectrum caspase inhibitor abolished myocardial apoptosis and improved cardiac function in the immunization rats. Conclusion: Our results demonstrated that stimulation with the antibody against β 1 ‐AR‐EC II induces cardiomyocyte apoptosis in vivo contributing to cardiac dysfunction, and suggest that anti‐apoptotic treatments may be a novel strategy in reducing multiple organ injury associated with immune response.