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Functional and structural characterization of anti-beta1-adrenoceptor autoantibodies of spontaneously hypertensive
Gerd Wallukat1, Svenia Podlowski, Eberhard Nissen
1Max Delbrück Centrum für Molekulare Medizin, Berlin, Germany. gwalluk@mdc.berlin.de
Abstract:
Eighteen month old spontaneously hypertensive rats (SHR-rats) showed myocardial dysfunction and autoantibodies directed against the beta1-adrenoceptor similarly as known in human dilated cardiomyopathy or Chagas' disease. The agonist-like antibodies were able to activate the beta1-adrenoceptor mediated signal transduction cascade in cultured rat cardiomyocytes and induced a long-lasting stimulatory effect resulting in a harmful adrenergic overdrive. The antibodies recognized an epitope of the second extracellular loop of the beta1-adrenoceptor identical to that epitope identified in Chagas' disease. In conclusion, our assumption is supported that old SHR-rat are an useful animal model for investigating the role of anti-beta1-adrenoceptor antibodies in the induction of human cardiomyopathy.
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