MYOCARDIAL INJURY DUE TO G-PROTEIN COUPLED RECEPTOR-AUTOIMMUNITY

One of the main mechanisms for dilated cardiomyopathy is likely to be autoimmune mediated myocardial damage. So far, a variety of autoantibo dies have been detected against a number of putative autoantigens in t he sera of patients with dilated cardiomyopathy. A growing body of stu dies have confirmed that autoantibodies against the second extracellul ar loop of beta(1)-adrenoceptors and M2-muscarinic receptor are presen t in 30-40% of patients with dilated cardiomyopathy. These anti-beta(1 )-adrenoceptor and anti-M2-muscarinic receptor antibodies can not only decrease the binding sites of antagonist but also recognize the targe t receptors. Moreover, these two autoantibodies possess an 'agonist-li ke' stimulatoty effect on the target receptors. In order to elucidate whether the autoantibodies against these autoimmune epitopes play an i mportant role in the pathogenesis of dilated cardiomyopathy, we immuni zed rabbits over a period of one year with synthetic peptides correspo nding to the second extracellular loop of the beta(1)-adrenoceptor and the M2-muscarinic receptor. These peptides induced morphological chan ges in the heart similar to those found in dilated cardiomyopathy. The se clinical and experimental findings suggest that these receptor auto antigens are of pathogenic importance in the development of dilated ca rdiomyopathy in vivo.