التفاصيل البيبلوغرافية
| العنوان: |
Phenotype of early cardiomyopathic changes induced by active immunization of rats with a synthetic peptide corresponding to the second extracellular loop of the human β1-adrenergic receptor. |
| المؤلفون: |
Buvall, L., Bollano, E., Chen, J., Shultze, W., Fu, M. |
| المصدر: |
Clinical & Experimental Immunology; Feb2006, Vol. 143 Issue 2, p209-215, 7p, 2 Charts |
| مصطلحات موضوعية: |
CARDIOMYOPATHIES, BETA adrenoceptors, RATS, IMMUNIZATION, AUTOIMMUNITY, AUTOANTIBODIES, MESSENGER RNA |
| مستخلص: |
In the failing human heart, due to idiopathic dilated cardiomyopathy, it has been suggested that the β1-adrenergic receptor (β1AR) is a potential pathogenic autoantigen. The aim of the present study was to investigate whether immunization of rats with a synthetic peptide corresponding to the second extracellular loop of the β1AR (β1AR ECII) was able to induce the early stage of cardiomyopathy and also to investigate immunological and receptor functional parameters at a transcriptional level to permit insights into the autoimmune mechanism in cardiomyopathy. Eleven Whistar Fur rats were immunized with a β1AR ECII peptide (H26R) once a month during 12 months and seven control rats were injected with vehicle according to the same procedure used for the immunized group. Cardiac function, β1AR autoantibodies and their functional effects on cardiomyocytes were analysed. β1AR receptor signalling, immunological and cardiomyocyte stretch markers were determined on transcriptional level. In H26R immunized rats, β1AR autoantibodies were shown to be present and functionally active, cardiac functions in terms of fractional shortening were decreased and β1-adrenergic receptor kinase (GRK2) mRNA were increased compared with the control group. These data have shown that immunization of rats with a putative antigenic peptide was able to induce an early stage phenotype of cardiomyopathy in the form of cardiac dysfunction and up-regulation of GRK2 as the first step in the desensitization process of the β1AR, implying the pathological importance of the β1AR autoantibody. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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