Mechanism of anti-β-adrenoceptor antibody mediated myocardial damage in dilated cardiomyopathy

Abstract

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 β_i-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.

Keywords

antibodies / β-adrenoceptor / cytoplasmic free calcium / fura-2/AM / dilated cardiomyopathy

References

[1] LimasC J, LimasC. Immune-mediated modulation of β-adrenoceptor function in human dilated cardiomyopathy. Clin Immunnol Immunopathol, 1993, 68: 204-204

[2] WollenbergerA, WallukatG. 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): 67-67

[3] WallukatG, MorwinskiM, KowalK, et 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): 178-178

[4] RosenbaumM B, ChialeP A, SchejtmanD, et al.. Antibnodies to Betaadrenergic receptors disclosing agonist-like properties in idiopathic dilated cardiomyopathy and Chargas heart disease. J Cardiovasc Electrophysiol, 1994, 5: 367-367

[5] MagnussonY, WallukatG, WaagsteinF, et al.. Autoimmunity in idiopathic dilated cardiomyopathy. Characterization of antibodies against the βadrenoceptor with positive chronotropic effect. Circulation, 1994, 89: 2760-2760

[6] 1994,74:375

[7] ADP/ATP 1995, 11:211

[8] ADP/ATP, 1995, 11:335

[9] BahouthS W, MalbonC C. Human β-adrenergic receptors: Simultaneous purification of β₁ and β₂-adrenergic receptor peptides. Biochem J, 1987, 248: 557-557

[10] KaumannA J. Some aspects of heart beta adrenoceptor function. Cardiovasc Drugs Therapy, 1991, 5: 549-549