Agonistic anti-beta(1)-adrenergic receptor autoantibodies from cardiomyopathy patients reduce the beta(1)-adrenergic receptor expression in neonatal rat cardiomyocytes

Article

关键词: BETA-ADRENERGIC-RECEPTOR;    MESSENGER-RNA LEVELS;    IDIOPATHIC DILATED CARDIOMYOPATHY;    HUMAN VENTRICULAR MYOCARDIUM;    FAILING HUMAN HEART;    C-6 GLIOMA-CELLS;    DOWN-REGULATION;    BETA(2)-ADRENERGIC RECEPTOR;    BETA-1-ADRENERGIC RECEPTOR;    SHORT-TERM;   

DOI  :  10.1161/01.CIR.98.22.2470

来源: SCIE

【 摘 要 】

Background-Autoantibodies directed against the beta(1)-adrenergic receptor have been described in patients with dilated cardiomyopathy. These autoantibodies exert an agonistic, chronotropic effect on spontaneously beating cultured neonatal rat cardiomyocytes. We studied the effect of such antibodies on beta(1)-adrenergic receptor expression. Methods and Results-Cardiomyocytes were incubated with either the beta-adrenergic agonist isoproterenol or autoantibodies for 72 hours. beta-Adrenergic receptor expression was studied on the mRNA level with semiquantitative reverse transcription-polymerase chain reaction and on the protein level with immunoblotting. Isoproterenol downregulated both mRNA and beta(1)- and beta(2)-adrenergic receptor protein subtypes, whereas the anti-beta(1)-adrenergic receptor autoantibodies decreased only the beta(1)-adrenergic receptor mRNA and protein. Long-term incubation of cultured cardiomyocytes with isoproterenol or the anti-beta(1)-adrenergic receptor autoantibodies reduced the acute stimulatory effect of isoproterenol on the myocytes. These effects were prevented by incubating the cells with isoproterenol in the presence of propranolol or with anti-beta(1)-adrenergic receptor autoantibodies in the presence of bisoprolol. Bisoprolol also abolished the reduction of the beta(1)-adrenergic receptor expression caused by longer-term incubation with isoproterenol and the autoantibodies. Conclusions-We conclude that after longer-term treatment with the anti-beta(1)-adrenergic receptor autoantibodies, the rat cardiomyocytes showed a beta-adrenergic receptor expression similar to that observed in failing hearts from patients with dilated cardiomyopathy.

【 授权许可】

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