Phenotype of early cardiomyopathic changes induced by active immunization of rats with a synthetic peptide corresponding to the second extracellular loop of the human beta1-adrenergic receptor

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Item Type:	Article
Title:	Phenotype of early cardiomyopathic changes induced by active immunization of rats with a synthetic peptide corresponding to the second extracellular loop of the human beta1-adrenergic receptor
Creators Name:	Buvall, L., Bollano, E., Chen, J., Shultze, W. and Fu, M.
Abstract:	In the failing human heart, due to idiopathic dilated cardiomyopathy, it has been suggested that the {beta}1-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 {beta}1AR ({beta}1AR 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 {beta}1AR 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, {beta}1AR autoantibodies and their functional effects on cardiomyocytes were analysed. {beta}1AR receptor signalling, immunological and cardiomyocyte stretch markers were determined on transcriptional level. In H26R immunized rats, {beta}1AR autoantibodies were shown to be present and functionally active, cardiac functions in terms of fractional shortening were decreased and {beta}1-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 {beta}1AR, implying the pathological importance of the {beta}1AR autoantibody.
Keywords:	Beta1-Adrenergic Receptor, Cardiac Function, Cardiomyopathy, Immunization
Source:	Clinical and Experimental Immunology
ISSN:	0009-9104
Publisher:	Blackwell Publishing
Volume:	143
Number:	2
Page Range:	209-215
Date:	February 2006
Official Publication:	https://doi.org/10.1111/j.1365-2249.2005.02986.x
PubMed:	View item in PubMed

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