Antibodies against β1-adrenoceptor can be detected in serum of patients with dilated cardiomyopathy (DCM), which have β-agonist-like activity, and induce a positive chronotropic effect on cardiac myocytes by its persistence at full strength. Effects of the antibodies against β-adrenoceptor from sera of patients with DCM on myocardial cytotoxicity and cytoplasmic free Ca2+-concentration ([Ca2+]i) were observed in the cultured single layer SD rat ventricular cells by using the cytotoxicity assay and fluorescent Ca2+- indicator fura-2/AM. The positive sera of the anti-β-adrenoceptor antibodies from patients with DCM markedly enhanced myocardial [Ca2+]i. Betaloc, a βi-receptor blocker, might inhibit the increase of the antibody-mediated myocardial [Ca2+]i, and the sera from healthy donors had no effect on myocardial [Ca2+]i. Our results suggest that the anti-β-adrenoceptor antibody might increase myocardial [Ca2+]i and result in myocardial damage. The antibodies might activate receptor-gating [Ca2+]-channel, thereby causing myocardial [Ca2+]i rise and calcium overload. Early use of betaloc is recommended in the treatment of dilated cardiomyopathy.
This is a preview of subscription content, log in to check access
Limas C J, Limas C. Immune-mediated modulation of β-adrenoceptor function in human dilated cardiomyopathy. Clin Immunnol Immunopathol, 1993, 68:204CrossRefGoogle Scholar
Wollenberger A, Wallukat G. Anti-β-adrenoceptors auto-antibodies from patients with myocarditis and dilated cardiomyopathy: β-adrenergic agonist activity without desensitization. J Mol Cell Cardiol, 1989, 21(Supp I):67CrossRefGoogle Scholar
Wallukat G, Morwinski M, Kowal Ket al. Autoantibodies against the β-adrenergic receptor in human myocarditis and dilated cardiomyopathy: β-adrenergic agonism without desensitization. Eur Heart J, 1991, 12(Suppl D):178PubMedGoogle Scholar
Rosenbaum M B, Chiale P A, Schejtman Det al. Antibnodies to Betaadrenergic receptors disclosing agonist-like properties in idiopathic dilated cardiomyopathy and Chargas heart disease. J Cardiovasc Electrophysiol, 1994, 5:367PubMedCrossRefGoogle Scholar
Magnusson Y, Wallukat G, Waagstein Fet al. Autoimmunity in idiopathic dilated cardiomyopathy. Characterization of antibodies against the βadrenoceptor with positive chronotropic effect. Circulation, 1994, 89:2760PubMedGoogle Scholar