Myocardial injury due to G-protein coupled receptor-autoimmunity

Abstract

One of the main mechanisms for dilated cardiomyopathy is likely to be autoimmune mediated myocardial damage. So far, a variety of autoantibodies have been detected against a number of putative autoantigens in the sera of patients with dilated cardiomyopathy. A growing body of studies have confirmed that autoantibodies against the second extracellular loop of beta 1-adrenoceptors and M2-muscarinic receptor are present 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 target receptors. Moreover, these two autoantibodies possess an 'agonist-like' stimulatory effect on the target receptors. In order to elucidate whether the autoantibodies against these autoimmune epitopes play an important role in the pathogenesis of dilated cardiomyopathy, we immunized rabbits over a period of one year with synthetic peptides corresponding to the second extracellular loop of the beta 1-adrenoceptor and the M2-muscarinic receptor. These peptides induced morphological changes in the heart similar to those found in dilated cardiomyopathy. These clinical and experimental findings suggest that these receptor autoantigens are of pathogenic importance in the development of dilated cardiomyopathy in vivo.