Mechanism of anti-beta-adrenoceptor antibody mediated myocardial damage in dilated cardiomyopathy.
Antibodies against beta(1)-adrenoceptor can be detected in serum of patients with dilated cardiomyopathy (DCM), which have beta-agonist-like activity, and induce a positive chronotropic effect on cardiac myocytes by its persistence at full strength. Effects of the antibodies against beta-adrenoceptor from sera of patients with DCM on myocardial cytotoxicity and cytoplasmic free Ca(2+)-concentration ([Ca2+]i) were observed in the cultured single layer SD rat ventricular cells by using the cytotoxicity assay and fluorescent Ca(2+)-indicator fura-2/AM. The positive sera of the anti-beta-adrenoceptor antibodies from patients with DCM markedly enhanced myocardial [Ca2+]i. Betaloc, a beta(1)-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-beta-adrenoceptor antibody might increase myocardial [Ca2+]i and result in myocardial damage. The antibodies might activate receptor-gating Ca(2+)-channel, thereby causing myocardial [Ca2+]i rise and calcium overload. Early use of betaloc is recommended in the treatment of dilated cardiomyopathy.
Liao
Y
Y
Institute of Cardiovascular Diseases, Tongji Medical University, Wuhan.
Cheng
L
L
Tu
Y
Y
Zhang
J
J
Dong
J
J
Li
S
S
Tian
Y
Y
Peng
Y
Y
D000328:Adult; D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D001693:Biological Transport, Active; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels; D002311:Cardiomyopathy, Dilated / Q000276:immunology*; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000276:immunology*
D001323:Autoantibodies; D015220:Calcium Channels; D011943:Receptors, Adrenergic, beta; D002118:Calcium